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    You are here : Home » MS Research News » Drugs » Disease Modifying Drugs » Disease Modifying Drugs Ongoing Research » BETASERON® (BETAFERON®)

    BETASERON® (BETAFERON®)

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    Benefit seen with interferon lasts into progressive MS

    InterferonPatients with primary progressive multiple sclerosis (PPMS) who took interferon-beta-1b for two years in a randomized trial continued to show improvement relative five years later, Spanish researchers said.

    Although the patients received no further interferon treatment after the randomized trial ended, those who had taken the drug during the study had both better scores for functional outcomes and better MRI evaluations at follow-up than those who had been treated with placebo, according to Xavier Montalban, PhD, of Autonomous University of Barcelona, and colleagues.

    In addition, the study suggested that interferon-treated patients with better than average benefit during the trial showed less disability progression when they went off the drug, they wrote in the November issue of Archives of Neurology.

    That finding, Montalban and colleagues said, "provides some evidence that immunomodulation could be explored still further in the search for an effective treatment for PPMS."

    There is currently no established treatment for PPMS. The clinical symptoms are similar to those of the more common relapsing-remitting form of the disease (RRMS), but PPMS has been less responsive to treatments effective against RRMS.

    Two-year results from the 73-patient randomized trial, published in 2009, indicated that interferon-beta-1b did not significantly delay disability progression as measured with EDSS scores, but the drug did show some benefit in certain functional outcomes and MRI variables.

    Montalban and colleagues followed participants for another five years. The current report includes data on functional outcomes for 59 of the original patients and MRI variables for 50, about equally divided between the interferon and placebo groups.

    At the five-year evaluation, the interferon-treated patients still showed no improvement in EDSS-scored disability progression relative to the placebo group.

    But interferon treatment was associated with significantly better performance on a test of manual dexterity and another involving cognitive ability, the latter being part the Brief Repeatable Battery of Neuropsychological Tests:

    Nine-hole peg test score: interferon 0.32; placebo -0.90 (P=0.02)
    Word list generation: interferon 19.0; placebo 11.5 (P<0.001)
    There were also weak trends favoring the interferon group for other functional evaluations, including scores on the Sickness Impact Profile, tests of spatial recall, and symbol digit manipulation.

    MRI variables also trended toward better numbers for the patients who had received interferon. Mean T1 and T2 lesion volumes at the five-year follow-up were about 40% lower in the interferon-treated patients, although large variations among patients kept the differences from reaching statistical significance.

    One significant difference was in brain atrophy tracked since the study began. The brain parenchymal fraction declined by 1.78% in the interferon group versus 3.16% in the placebo-treated patients (P=0.004).

    Montalban and colleagues also reported a significant correlation between MRI results during the two-year treatment phase and changes in EDSS disability scores after the trial ended (r=0.36, P=0.004.)

    The researchers stopped short of endorsing interferon-beta-1b treatment for PPMS patients, since the randomized trial results were not particularly impressive.

    Instead, they suggested that treatments altering immune activity should be investigated further in the disorder, despite the disappointing findings of earlier trials with various forms of interferon as well as rituximab (Rituxan) and glatiramer acetate (Copaxone).

    Limitations of the current study included the lack of data on some patients and the absence of gadolinium-enhanced MRI scans.

    Montalban and colleagues also noted that patients who dropped out of the study were "probably the most disabled ones."

    The study was funded by Bayer Schering's Spanish affiliate.

    Study authors reported serving as consultants or speakers for Serono, sanofi, Novartis, Teva, Biogen Idec, Bayer Schering, Almirall, Lilly, and Bracco, as well as receiving research support from several of these companies.

    Full Article - "Interferon beta-1b for the treatment of primary progressive multiple sclerosis: five-year clinical trial follow-up" Arch Neurol 2011; 68: 1421-27.

    Source: MedPage Today © 2011 Everyday Health, Inc. (16/11/11)

    Study revisits first clinical trial to treat MS decades later

    Disease Modifying DrugsTracking down nearly all 372 multiple sclerosis patients involved in a pivotal clinical trial of a drug decades ago has allowed a group of researchers from several institutions, led by professors at the University of California, San Francisco (UCSF) and the University of Chicago, to a surprising discovery.

    The clinical trial,  conducted in the late 1980s, involved the biotech drug interferon beta-1b  – an injectable protein that in 1993 became the first pharmaceutical approved by the U.S. Food and Drug Administration for treating multiple sclerosis.

    Now, more than two decades later, the researchers are reporting that the people who received interferon in the trial, as opposed to a placebo, were only about half as likely to have died in the decades since.

    "This is a very significant reduction in mortality," said UCSF neurologist Douglas Goodin, MD, who presented a poster on the study last week with his coauthor Anthony Reder of the University of Chicago at the 63rd Annual Meeting of the American Academy of Neurology in Hawaii.

    Clearly there is something profound reflected in the data, the study authors said, but they could not say what exactly accounts for the difference. After all, the study was over by the early ’90s and in the decades since all of the patients likely took drugs other than interferon beta-1b, since within a decade three other drugs also were approved for treating MS.

    Data Graph

    This graph shows that data gathered 21 years after the original trial ended shows a significant long-term survival advantage for people who received injections of interferon beta-1b (blue line) over people who received placebo (black line).


    A Disease of the Nervous System

    Multiple sclerosis is an autoimmune disease that causes recurrent attacks on the nervous system, inducing inflammatory lesions in the brain. These lesions sometimes cause people with MS to become temporarily blind or lose control of their bladders. Often the lesions disappear and the person with MS recovers – until the next attack.

    "It doesn't always get better," said Goodin, director of the Multiple Sclerosis Center at UCSF Medical Center. "Over time people may become permanently disabled because of these lesions."

    Interferon beta-1b works by exerting an anti-inflammatory effect yet, even though it has been around for many years now, there have never been any long-term studies of its effect on human health.

    What the new data indicate, said Goodin and Reder, is significant long-term survival advantage to taking the drug. Now they are investigating possible biological explanations of this difference.

    The presentation "Mortality Outcomes for Interferon Beta-1b vs Placebo 21 Years Following Randomization" was authored by Douglas Goodin, Anthony Reder, George Ebers, Gary Cutter, Marcelo Kremenchutzky, Joel Oger, Dawn Langdon, Mark Rametta, Karola Beckmann, and Volker Knappertz. Authors are from the original 11 North American clinical trial sites and Bayer Pharmaceuticals.

    Source: University of California © 2011 The Regents of the University of California.(27/04/11)

    Betaferon Extends MS Patient Lives, 21-Year Follow-Up Study Finds

    BetaferonBetaferon multiple sclerosis treatment helped patients live longer when taken soon after the onset of the disease in a study researchers said is the first to show such a drug extends patients’ lives.

    Patients who got betaferon soon after diagnosis were 39 percent less likely to be dead more than two decades later than those who were given a placebo, researchers said in a study released today at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Gothenburg, Sweden.

    Long-term data establishing effectiveness and safety may help differentiate older MS treatments like the Bayer drug, approved in the U.S. in 1993, from newer treatments such as Novartis AG’s pill Gilenya, lead researcher Anthony Reder, director of the University of Chicago MS Clinic, said in a conference call with reporters.

    “The number I’m giving you today is a bird in the hand, here, with a very prominent effect,” Reder said.

    Merck KGaA’s Rebif and Biogen Idec Inc.’s Avonex, both beta interferons in the same family as the Bayer drug, might also be expected to show a similar survival benefit, Reder said. Merck, based in Darmstadt, Germany, and Cambridge, Massachusetts-based Biogen Idec haven’t tested survival over such a long time window, he said. The data isn’t likely to come up in a shorter trial because patients may live for a long time with the debilitating neurological disease, he said.

    With funding from Bayer, based in Leverkusen, Germany, Reder and other researchers tracked down all but six of the 372 patients who participated in a betaferon trial in 1988, before the drug was approved in the U.S. or Europe.

    Initial Trial

    In the initial trial, 249 patients were given a dose of betaferon, while 123 were assigned to receive a placebo. Patients were treated for a median of 3.8 years, with a maximum of 5.1 years, before exiting the trial and getting a licensed treatment, if any.

    Bayer has said it expects sales of betaferon, sold in the U.S. as betaseron, to drop between 5 percent and 10 percent this year due to competition from generic copies and newer medicines. The therapy was Bayer’s second-biggest-selling drug last year, behind the Yaz family of birth-control pills, with 1.21 billion euros ($1.7 billion) in sales.

    Novartis’s Gilenya went on sale in the U.S. this month after being approved Sept. 22.

    Source: Bloomberg ©2010 BLOOMBERG L.P (16/10/10)

    Study supports long-term safety profile of Betaferon® for Multiple Sclerosis over 16 years

    BetaferonResults from the 16-year follow-up to the pivotal Betaferon® (interferon-beta-1b) trial, published today in the journal Neurology, provide the longest and most complete patient follow-up data and support the long-term safety profile of Betaferon in multiple sclerosis (MS).

    Results demonstrated that no new or unexpected adverse events (AEs) emerged with long-term therapy, and the observed treatment-related AEs decreased over time.

    "These data confirm that Betaferon has a favorable safety and tolerability profile," said Anthony T. Reder, Professor of Neurology at the University of Chicago and lead study author. "Over the years, healthcare professionals have been able to greatly reduce treatment-related adverse events and increase patients? adherence to Betaferon therapy with dose escalation at initiation of therapy and the routine use of an autoinjector and co-medication with non-steroidal anti-inflammatory drugs (or NSAIDs)."

    Interestingly, preliminary findings suggest that there was improved survival for patients assigned to Betaferon in the pivotal trials (94.6 percent in those who received 250µg and 91.7 percent in patients treated with Betaferon 50µg) compared with placebo (81.7 percent).

    MS is a chronic condition that requires treatment with a medication that combines efficacy with a safety profile that is manageable and predictable even over the long term,? said Leslie Donato, Vice President, Neurology, Bayer. ?The results of the 16-year long-term study add to the wealth of data supporting Betaferon?s benefit-to-risk profile. We look forward to seeing additional outcomes from the 20-year follow-up study.?

    About the study

    The 16-Year Long-Term Follow-Up (LTF) was a multicenter, cross-sectional, observational study of outcomes in patients with relapsing-remitting MS (RRMS) who participated in the pivotal Betaferon study. For the study, the investigators identified more than 88 percent of the patients enrolled in the original pivotal trials for whom vital status information (living or deceased) was available. Nearly 70 percent (260 people) were evaluated by a neurologist at clinical visits. Consolidating the three pivotal trial arms, patients had a median treatment exposure duration of 7.9 years, or 2,000 patient-years of Betaferon therapy.

    Typical AEs experienced among patients receiving Betaferon continuously for two years prior to the LTF visit (n=69) included flu-like symptoms (31.9 percent), fever (21.7 percent), headache (27.5 percent), injection-site reactions (erythema, pain, or swelling, 81.2 percent), malaise (23.2 percent), myalgia (21.7 percent) or elevated liver transaminases (10.1 percent). No skin necrosis was recorded.

    Differences in depression rates at LTF between patients originally assigned to placebo relative to those initially randomized to Betaferon were non-significant. Depression rates in patients who received Betaferon for and #8805;80 percent of the time during the pivotal study were 25.0 percent, and during the last two years of LTF were 32.1 percent (p = 0.53). These are well within the known range found in MS populations and the authors conclude that the study found no evidence linking depression to Betaferon.

    Mild lymphopenia and elevated liver enzymes were detected in the pivotal trial, but were seldomly observed at LTF. No case of chronic liver disease was identified throughout 16 years of follow-up. AEs associated with Betaferon treatment decreased over time, and were less frequent in the last two years of LTF compared with treatment during the pivotal trial.

    Source Bayer Healthcare AG (09/06/10)

    Clinical effect of neutralizing antibodies to interferon beta that persist long after cessation of therapy for Multiple Sclerosis

    InterferonOBJECTIVES: To confirm that neutralizing antibodies (NAb) to interferon beta can persist after therapy withdrawal and to evaluate whether persisting NAb are associated with a worse clinical disease course in multiple sclerosis (MS).

    DESIGN: Retrospective study. SETTING: Tertiary referral center in the Netherlands. Patients A total of 71 patients with relapsing-remitting multiple sclerosis treated with interferon beta in the past.

    MAIN OUTCOME MEASURES: Persisting NAb after therapy withdrawal were tested using the cytopathic effect assay. Patients with and without persisting NAb were compared on several outcomes: the change in annualized relapse rate from prior to interferon beta treatment initiation to after cessation of treatment, time to sustained disability on the Kurtzke Expanded Disability Status Scale, and the use of disease-modifying treatments after cessation of treatment with interferon beta.

    RESULTS: Seventeen of 71 patients (24%) tested NAb positive after a median interval of 25 months (interquartile range, 10-51 months) after interferon beta treatment cessation. Eleven of these 17 patients (15%) were high-titer NAb positive (>150 10-fold reduction units per mL). Persisting NAb were associated with an increase in the annualized relapse rate (P = .04) and a reduction in time to reach a sustained Expanded Disability Status Scale score of 6.0, ie, the need for unilateral assistance to walk 100 m (P = .02). Moreover, NAb-positive patients were treated with second-line therapy significantly more often, especially mitoxantrone (P = .006).

    CONCLUSION: Anti-interferon beta NAb can persist after interferon beta treatment withdrawal and are associated with overt clinical disease activity. This is made apparent by an increase in relapse rate and faster disability progression and is supported by the observed need for more aggressive therapy after interferon beta treatment cessation. Prospective studies are warranted to confirm these results.

    Source: Pubmed PMID: 20142519 (22/02/10)

    A single-centre, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis

    Interferon beta-1bInflammation and neurodegeneration may have differential impacts on disease evolution in the different forms of multiple sclerosis. However, a beneficial effect of immunomodulatory drugs should not be ruled out in primary progressive multiple sclerosis.

    Our aim is to investigate the safety and efficacy of interferon beta-1b in primary progressive multiple sclerosis.

    We conducted a double-blind, stratified, randomized, parallel group, phase II pilot study where patients with primary progressive multiple sclerosis or ‘transitional’ forms of multiple sclerosis received interferon beta-1b at doses of 8 MIU or placebo for 24 months.

    The main objective of the study was to investigate the safety and tolerability of interferon beta-1b.

    The primary efficacy variable was the time to neurological deterioration (Expanded Disability Status Scale) confirmed at 3 months.

    Seventy-three patients were included and three dropped out the study. More patients in the treatment arm had at least one related adverse event (94.4% versus 45.9%; p < 0.001); no other significant differences in safety endpoints were observed.

    Time to neurological deterioration was not different between trial arms (log-rank test, p = 0.3135). Statistically significant differences favouring treatment were observed for the Multiple Sclerosis Functional Composite score at several timepoints, T1 and T2 lesion volume changes at 12 and 24 months, mean number of active lesions and proportion of patients with active lesions at 24 months.

    We conclude that interferon beta-1b is safe and well tolerated in patients with primary progressive multiple sclerosis and transitional multiple sclerosis.

    Positive effects of interferon beta on secondary clinical and magnetic resonance imaging outcomes were observed, but a beneficial effect on Expanded Disability Status Scale progression was not demonstrated.

    X Montalban, J Sastre-Garriga, M Tintoré, L Brieva, F X Aymerich, J Río, J Porcel, C Borràs, C Nos, and A Rovira
    Unitat de Neuroimmunologia Clínica, Multiple Sclerosis Centre of Catalonia

    Source: Multiple Sclerosis 2009, doi:10.1177/1352458509106937 (02/10/09)

    Five-year data confirm that early treatment with Betaseron(R) at first sign of disease can delay progression to MS

    Disease Modifying Drugs

    Data from its BENEFIT (BEtaseron in Newly Emerging multiple sclerosis For Initial Treatment) study confirm that early initiation of Betaseron(R) (interferon beta-1b) treatment in patients with a first event suggestive of multiple sclerosis (MS) significantly delayed the onset of clinically-definite MS (CDMS) by 37 percent (p=0.003) and McDonald MS by 45 percent (p<0.0001) over five years compared to delayed treatment.

    The results confirm a continued benefit of initiating treatment with Betaseron shortly after the first event.(1) These five-year findings from the BENEFIT study were presented today at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRIMS).

    "The BENEFIT five-year results are the first and only prospectively planned data to confirm a continuous benefit over five years when treatment is initiated shortly after the earliest sign of MS," said Dr. Mark Freedman, Professor of Neurology at the University of Ottawa and investigator of the study. "These results confirm that treatment with Betaseron after the first MS event or attack can reduce the risk of developing MS over five years compared to delayed treatment."

    The study also demonstrated that early treatment with Betaseron had a beneficial effect on cognition that became even more pronounced over time. At five years, patients with early treatment had better cognitive function (mean PASAT score) compared to patients with delayed treatment (p= 0.0045).(1) PASAT, or the Paced Auditory Serial Addition Test, is a widely accepted tool that measures intellectual function and cognition.

    "Changes in cognitive function have important implications for a patient's quality of life. Changes in cognition, along with fatigue, can be a reason for early departure from the workforce. Patients treated early with Betaseron fared better in tests of cognitive function compared to those with delayed treatment, which is good news for people with MS," Dr. Freedman said.

    The BENEFIT study was the first to demonstrate a reduction in the risk of confirmed EDSS progression, as measured by the Expanded Disability Status Scale (EDSS), with early versus delayed treatment. This effect first appeared at year three, with a significant risk reduction of 40 percent (p=0.022).(2) Over five years, a nominal risk reduction of 24 percent (p=0.177) was observed for early treatment compared to delayed treatment. This difference over five years was not statistically significant.(1)

    The key findings from the BENEFIT five-year study showed that:(1)

    -- Starting Betaseron after the first clinical event delayed the development of CDMS by more than two years (750 days) in the 40th percentile.

    -- Patients treated early with Betaseron had a greater reduction in relapse rate over five years compared to patients with delayed treatment, (0.21 versus 0.27) despite the latter receiving at least three years of treatment after the second attack or after two years (p=0.014; Poisson model). This effect was mainly due to the differences between the groups during the first two years.

    -- Early treatment significantly reduced the development of newly active brain lesions (new or enlarging T2 lesions, Gd-enhancing lesions) compared to delayed treatment (p=0.0062).

    -- In the BENEFIT study there was a high level of study completion of Betaseron by patients with the earliest signs of MS. Two-thirds of patients (67 percent) in the early treatment group continued on Betaseron for five years.

    -- Patients consistently reported a high Health-Related Quality of Life over the five-year study period.

    Adverse events (AEs) reported at five years were consistent with the product label.

    (1) MS Freedman, L Kappos, CH Polman, et al. Impact of Early Interferon beta-1b Treatment on Disease Evolution Over 5 Years in Patients with a First Event Suggestive of Multiple Sclerosis. World Congress on Treatment and Research in Multiple Sclerosis 2008.

    SOURCE Bayer HealthCare Pharmaceuticals Inc. (22/09/08)

    BRIGHT Results Show Less Pain and Higher Patient Satisfaction with Betaseron than with Rebif
    Study shows injection site pain can negatively influence patient satisfaction with treatment.

    Patients with relapsing-remitting multiple sclerosis (MS) treated with 250 mcg Betaseron (interferon beta-1b) experienced less injection site pain and fewer injection site reactions than those treated with 44 mcg Rebif. Moreover, among those who experienced injection site pain, significantly more patients on Rebif versus Betaseron said that pain negatively influences their satisfaction with treatment. These results from the BRIGHT (Betaseron(R) versus Rebif(R) Investigating Higher Tolerability) study were published in this month's issue of Multiple Sclerosis.

    "BRIGHT is the first large-scale study to compare injection site reactions and pain with two high-dose interferons," said Dr. Karl Baum, an author of the study, and Chief of Neurology, Hennigsdorf Clinic, Hennigsdorf, Germany. "Injection site reactions and pain occur in many patients using injection interferon therapies, and these results show that reducing pain helps to improve their satisfaction with treatment. This is important because greater patient satisfaction may improve patient adherence to therapy and consequently, its effectiveness."

    "MS is a chronic disease that requires long-term treatment. An effective therapy with high tolerability and comprehensive patient support programs, like Betaseron, can greatly aid patients in achieving better outcomes," said Ludger Heeck, Ph.D., vice president and general manager, Specialized Therapeutics, Bayer HealthCare Pharmaceuticals. "The results of the BRIGHT study confirm the importance of good tolerability in achieving high patient satisfaction."

    The prospective, non-randomized, observational study compared Betaseron (interferon beta-1b) 250 mcg (subcutaneous, every other day) with Rebif (interferon beta-1a) 44 mcg (subcutaneous, three times weekly). The valid case population of the study included 445 patients who were treated with 15 consecutive injections of either Betaseron or Rebif for an observation period of four to five weeks.

    Significantly more Betaseron than Rebif patients were pain-free at all time points measured (immediately after injection, 30 minutes after injection, and 60 minutes after injection) over the course of 15 injections. Specifically, at 30 minutes after injection, 42.6 percent of Betaseron patients were pain-free, versus 19.7 percent of Rebif patients. At the conclusion of the study, more than half of the patients treated with Betaseron reported that they experienced no injection site reactions (51.8 percent) versus only one-third of the patients treated with Rebif (33.8 percent). The proportion of pain-free injections per patient was also greater with Betaseron than with Rebif at all time points. This was regardless of the needle size used for either product.

    Among participants who used autoinjectors (92 percent), there were significantly more pain-free patients in the Betaseron group versus the Rebif group at all time points (e.g., at 30 minutes after injection, 40.2 percent versus 16.2 percent). Additionally, more patients treated with Betaseron either had no pain or stated that their injection-site pain had no influence on their satisfaction with treatment, compared to those treated with Rebif (76.9 percent versus 64.1 percent).

    About the BRIGHT Study

    BRIGHT is a multicenter, international, non-randomized, prospective, observational study comparing the tolerability of Betaseron (250mcg) with Rebif (44mcg). The study included 454 patients (306 patients on Betaseron and 148 patients on Rebif) from 76 centers in 13 countries. Patients started treatment within three months prior to recruitment and were on the full dose of therapy. Nine of the patients were excluded because they did not take the full dose of either study drug. Although this was a non-randomized trial, patients were well matched for demographic and clinical characteristics.

    Patients self-injected and self-assessed injection site pain for 15 consecutive injections using a 0-100 mm visual analogue scale (VAS) diary immediately after injection, and 30 minutes and 60 minutes post-injection. Injection site reactions were professionally assessed and confirmed. To qualify for a "pain-free" status, a patient must have had an assessment of "no pain" (VAS=0) at all 15 injections.

    At the 15th injection, patients also were asked to assess how much injection site pain influenced their overall satisfaction with treatment. Patients who used an autoinjector were asked to assess its ease of use. The use of autoinjectors was recommended in the study.

    Source: Bayer HealthCare (09/11/07)

    Bayer dropping bid to market higher-dose MS treatment Betaferon
    Drug maker Bayer AG said Monday that it will take a charge of €152 million (US$218.64 million) from a decision to abandon plans to market a bigger dose of its multiple sclerosis treatment Betaferon.

    The company said that Bayer Schering Pharma AG, a unit set up after its nearly €16.9 billion acquisition of Schering AG in 2006, found in tests that a 500-microgram dose of Betaferon was no more effective in preventing relapses by patients who suffer from MS than the 250-microgram dose of Betaferon or that of Copaxone, which is produced by Teva Pharmaceutical Industries Ltd.

    Multiple sclerosis is an incurable disease where the immune system attacks the insulation of nerve fibers.

    Bayer said that because it won't seek permission from regulators to sell the higher dosage of Betaferon, also known as Betaseron, it would depreciate the costs of the study in the third quarter.

    Betaferon is a major drug for Bayer, accounting for some €500 million (US$719.2 million) in sales in the first six months of 2007. The company expects those sales to rise between 7 and 9 percent through 2008.

    Source: International Herald Tribune Copyright © 2007 the International Herald Tribune All rights reserved (29/10/07)

    Interferon Beta-1b in Combination With Azathioprine for Secondary Progressive Multiple Sclerosis
    The addition of azathioprine to standard treatment with interferon beta-1b (IFNbeta-1b) can be maintained over 2 years with only a mild increase in adverse effects in patients with secondary progressive multiple sclerosis (MS), according to results of a multicentre, randomised, comparative, double-blind study.

    Principal investigator Enrico Montanari, MD, Professor in Medicinal Psychology, Department of Internal Medicine, MS Centre, Fidenza, Italy, presented the study findings here on October 12 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    Secondary progressive MS is characterised by continuous worsening disability and can be accompanied by relapses after varying periods of relapsing-remitting disease. "With secondary progressive multiple sclerosis there remains no therapy, so from the background of other studies, we decided to investigate this combination therapy," Dr. Montanari said.

    The aim of the study was thus to assess the efficacy, safety and tolerability of azathioprine when added to IFNbeta-1b in patients with secondary progressive MS who had an incomplete response to IFNbeta-1b.

    The study provides an overall evaluation of illness stabilisation, with the primary endpoint being the variation in MS functional composite (MSFC) over the 2-year treatment period. Secondary endpoints were Expanded Disability Status Scale (EDSS) variability, quality of life (QOL) effects according to the MSQOL-54 Instrument, cytokine and neutralising antibodies levels, and safety.

    In the study, there was no significant difference between the two treatment groups in median scores on the EDSS in the previous 2 years. This evaluation considered the two treatment groups combined.

    The collective baseline characteristics of the 85 patients who entered the randomisation stage demonstrated a mean age of 46.2 years, and a male/female distribution of 36/64; the EDSS profile range was: 4.0, 30.7%; 4.5, 16.0%; 5.0, 18.7%; 5.5, 5.3%; 6.0, 18.7%; 6.5, 10.7%.

    There were no changes from baseline in the 6-month combined mean EDSS score variations over 2 years. Although there was an initial indication of a slight worsening in the MSFC score at 3 months (-0.10), the successive mean variations in the 6-month assessments showed maintenance of stable disease to 2 years (6, 12, 18, 24 months versus baseline): +0.02, +0.08, +0.10, +0.03, respectively.

    "With the MSFC that we are using, we also see that with the ambulation index and the arms and connection functions, the results are very interesting because there is a stabilisation of these [measures]," Dr. Montanari noted.

    Similarly, MSQoL-54 scores over 2 years of combined treatment show maintenance of a slight decrease from baseline scores at 6, 12, 18, and 24 months, in the composite scores of both physical health (-0.8, -1.0, -1.3, -0.8, respectively) and mental health (-2.0, -2.2, -2.1, -2.9, respectively).

    The researchers observed a mild increase in adverse events with azathioprine plus IFNbeta-1b compared with IFNbeta-1b alone that involved gastrointestinal problems, an increase in liver laboratory tests and leucopoenia.

    However, with a 63% rate of patient retention at the end of 2 years despite 82.4% of patients experiencing one or more adverse event, the results show good tolerability for the combination and are in line with data from other studies in patients with secondary progressive MS, the researchers noted.

    Therefore, although there is a mild increase in adverse effects in the azathioprine group, this combination of IFNbeta-1b and azathioprine demonstrates good stabilisation of clinical evolution in patients with secondary progressive MS, the researchers concluded.

    Source: Presentation title: ASPIRE: Interferon Beta-1b in Combination With Azathioprine for Secondary Progressive Multiple Sclerosis: A 2-Year, Double-Blind, Randomised, Multicentre, Pilot Study. Safety and Drop-Outs Data at 21 Months of Enrolment. Abstract P188 (16/10/07)

    Betaferon® treatment delays disability in early MS; strong efficacy not affected by neutralizing antibodies

    Betaferon® (interferon beta-1b) significantly delays the development of confirmed disability progression and the development of clinically definite multiple sclerosis (MS) in patients who are treated shortly after their first clinical MS event or “attack”. The presence of neutralizing antibodies (NAbs) does not affect the efficacy of early Betaferon® treatment. (1) This is according to new evidence from the landmark BENEFIT (BEtaferon in Newly Emerging multiple sclerosis For Initial Treatment) study presented today at the 23rd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

    Neutralizing antibodies can develop in MS patients being treated with any of the currently available immunomodulatory therapies. However, there has been debate over whether or not such antibodies can affect a treatment’s efficacy.

    “BENEFIT is a significant trial that provided the medical community with the first clear evidence on the value of treating patients with Betaferon® at the first clinical sign of MS to delay the accumulation of disability,” said Dr. Mark S. Freedman, Professor of Neurology at the University of Ottawa and investigator of the study. “The new data show that the presence of NAbs, regardless of the titre, does not reduce the efficacy of Betaferon® out to 3 years when administered after the first attack of MS. These results do not support the suggestion that the propensity for developing NAbs be a determining factor when making treatment decisions regarding Betaferon®.”

    The study presented at ECTRIMS shows that:

    • In patients starting treatment after a first MS attack, the efficacy of Betaferon® treatment in delaying the development of CDMS (Clinically Definite MS) and delaying confirmed disability was not affected by NAbs, regardless of NAb titre. Disability was measured using a validated, well-established scale called EDSS (Expanded Disability Status Scale) (2)

    • Of 277 patients treated early with Betaferon®, 31.8 percent (88) were tested positive at least once for NAbs (≥1:20 NU/ml). 16.6 percent (46) of 277 patients had NAb titres ≥1:100 NU/ml, and 9 percent (25) had titres ≥1:400 NU/ml.

    • 46.6 percent (41 of 88) of all patients with a documented NAb status reverted to NAb-negative status by Year 3. Among patients with higher NAb titres, 37 percent and 32 percent with NAb titres ≥1:100 NU/ml and ≥1:400 NU/ml, respectively, reverted to NAb-negative status by Year 3.

    "The data from the BENEFIT study continue to provide the medical community with important insights that will help to optimize the treatment of patients in the earliest stages of MS. These results support previously published, peer-reviewed research showing that the NAb status does not affect the efficacy of Betaferon®," said Darlene Jody, M.D., Senior Vice President and President of Bayer HealthCare’s Specialized Therapeutics Global Business Unit.

    Previously presented and published results of BENEFIT(3) demonstrated that over 3 years, patients treated with Betaferon® after the first MS attack had a 40 percent lower risk of developing confirmed disability and a 41 percent lower risk of developing clinically definite MS when compared to patients in whom treatment was delayed. No other MS therapy has demonstrated this effect in this early patient population.

    Around the world, Betaferon® is approved for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations, as well as for use in patients after the first attack of MS.

    About BENEFIT
    BENEFIT is a multi-center trial conducted at 98 sites in 20 countries and included patients presenting with a first clinical episode suggestive of MS and typical MRI findings. The primary outcome measures are time to diagnosis of CDMS (Clinically Definite MS), time to confirmed EDSS (Expanded Disability Status Scale) progression and patient reported Quality of Life outcomes (FAMS-TOI). A total of 468 patients were randomized to receive either 250 micrograms of interferon beta-1b (Betaferon®) every other day or placebo as a subcutaneous injection in a double-blind fashion. The placebo-controlled treatment period lasted up to 24 months or up to the time when patients experienced a second attack and were diagnosed with clinically definite MS. All study participants were then invited to participate in a follow-up study with Betaferon® to prospectively assess the impact of such early versus delayed treatment with Betaferon® on the long-term course of the disease for a total observation time of five years. The three-year results are from a pre-planned analysis.

    Previous published studies in this patient population have been criticized as less scientifically rigorous, because of their retrospective nature, unblinded assessments and the high number of patients lost to follow-up. The BENEFIT study was the first study in early MS patients designed to overcome these shortcomings.

    References
    (1) Freedman MS, Edan G, Hartung H-P, et al. Neutralising antibodies did not affect clinical outcomes after 3 years in the BENEFIT (BEtaferon in Newly Emerging multiple sclerosis For Initial Treatment) study. 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, 2007
    (2) Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52
    (3) Kappos L et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007 Aug 4; 370(9585): 389-97

    Source:  Bayer Schering Pharma (15/10/07)

    Early Betaseron(R) (interferon beta-1b) Treatment Delays Multiple Sclerosis

    Early treatment with the drug interferon slows the progression of multiple sclerosis (MS) in people with the first symptoms of the disease and reduces impairment, a Swiss study shows.

    The study of 468 people found that 37 percent of those who got every-other-day injections of Betaseron(R) (interferon beta-1b) progressed to full-blown MS over three years, compared to 51 percent of those who got inactive injections, according to the report in the Aug. 4 issue of The Lancet.

    Betaseron(R) (interferon beta-1b) treatment also reduced the progression of disability by 40 percent, the report said.

    Those numbers should help resolve a running debate about interferon treatment for people who experience a first episode of disability that warns of MS, said Dr. Ludwig Kappos, head of the MS-Research Group at University Hospital in Basel.

    "Other studies, including the early part of this one, showed that early treatment can delay occurrence of a second episode that allows one to make the diagnosis of multiple sclerosis," Kappos said. "But that the treatment had an impact on remaining ability was not clear. This study shows there is a difference, at least for some people."

    MS is a disorder of the central system in which the fatty tissue called myelin that surrounds nerve cells is destroyed. It is thought to be an autoimmune condition, wherein the body attacks its own tissue. Several laboratory-made versions of interferon are commonly used to treat the disease.

    To Patricia O'Looney, vice president for biomedical research at the National Multiple Sclerosis Society in New York City, an important aspect of this study is that it measured the progression of the disease precisely, patient by patient, using the well-established expanded disability status scale (EDDS). That scale goes in half-point steps from 0.5, the first sign of the disease, to 9.5, total disability.

    "What makes this study different is that it shows delay in progression on the EDDS scale, which other studies have not done," O'Looney said.

    The Swiss results "provide more evidence to support the value of early treatment," she said. "There has been disagreement about whether early treatment is beneficial. This provides additional evidence that early treatment delays progression on a disability scale."

    An accompanying editorial by Dr. Sean Pittock, a neurologist at the Mayo Clinic, praised the study, saying, "Kappos and colleagues have set a new standard against which future extension trials will be compared."

    But Pittock said the results of the trial should be "interpreted with care, because the magnitude of benefit, although significant, is clinically small. This follow-up should not be misconstrued as evidence for a 'treat all' approach."

    Kappos said he agreed with that assessment, but he noted that the trial covered only the first few years of a condition that could progress for decades. "In the early stages of the disease, the changes are minor," he said. "Later on, they can cause more severe problems. Changes that may look minor at an early stage take on greater importance."

    "Even if it is only marginal, a significant delay is still a delay," O'Looney said. "To someone with MS, even a marginal delay in the loss of the ability to walk is important."

    What the study results provide in the decision about treatment of a specific patient is "one more argument why it is important to have this treatment," Kappos said. "Then it is their decision. The treatment can cause side effects, and they have to weigh one against the other."

    But the side effects of interferon treatment generally are "benign," Kappos added. The treatment would be especially helpful to patients in whom silent brain lesions are found by MRI scans, he said.

    "This is an important argument to be considered by patients," Kappos said, and the trial results have changed the frame of that discussion. "Several years ago, neurologists hesitated to discuss it," he said, referring to early treatment. "Now, they can take the time to discuss it."

    Source: Forbes.com © 2007 Forbes.com LLC™   All Rights Reserved (03/08/07)

    Multiple Sclerosis Patients' Response to Interferon Beta Predicted by MRI: Presented at ENS
    Magnetic resonance imaging (MRI) of brain lesions at the beginning and after one year of treatment with Interferon beta (IFN-b) can help identify patients with multiple sclerosis (MS) who do not respond to IFN-b treatment, according to a study presented here at the 17th Meeting of the European Neurological Society (ENS).

    "Early identification of nonresponders may help neurologists in their decision about MS treatment," said Carlo Pozzilli, MD, Multiple Sclerosis Centre, S. Andrea Hospital, Rome, Italy. Dr. Pozzilli is head of the research team that performed the retrospective, post-marketing study involving 345 patients (101 men and 244 women, mean age at baseline 32.9±9.1 years) who had been treated with IFN-b for an average of 4.5 years (median 4, range 2-13). At the beginning of the study, subjects had a mean disease duration of 5.5±4.9 years and a median Expanded Disability Status Scale (EDSS) score of 1.5 (range 0-4.5).

    The researchers analysed EDSS scores and MRI scans taken at baseline and after one year of IFN-b treatment of all patients who completed the study. For subjects who discontinued IFN-b therapy, the final EDSS score was calculated at the last neurological assessment during IFN-b treatment.

    Patients with an increase of at least 1 point on the EDSS score (confirmed in two consecutive visits separated by a 6-month interval) were considered to have a "poor clinical response." Disease activity was determined based on the presence of gandolinium-enhancing (Gd-enhancing) lesions in post-contrast T1-weighted scans and on the accumulation of hyperintense lesions on T2-weighted images.

    Patients with a longer disease duration at the beginning of IFN-b treatment and a higher baseline EDSS than those with a stable level of disability were also more likely to have a poor response to IFN-b therapy (P =.04 and P <.001, respectively). A relapse within the first year of IFN-b therapy also was associated with an increased likelihood of poor response over the study period (OR 2, 95% CI 1.3-3.4; P =.003)

    The investigators found, however, that MRI data were even stronger predictors of long-term outcome, whereby both the presence of at least one Gd-enhancing lesion at 1-year (OR 3.4, 95% CI 2-5.7; P <.001) and an increase in T2 lesion burden (OR 8.6, 95% CI 5-14.5; P <.001) were related to a poor outcome.

    According to Dr. Pozzilli, "these results underline the importance of performing an MRI scan at the end of the first year of treatment with Interferon beta, in order to identify patients who do not respond to treatment."

    [Presentation title: Early Predictors of Poor Response to Interferon Beta Therapy in a Cohort of Relapsing-remitting Multiple Sclerosis. Abstract P294]

    Doctor's Guide Channel Copyright (c) 1995-2007 Doctor's Guide Publishing Limited. All rights reserved. (20/06/07)

    No Difference in MS Disease Activity Between Treatments
    Head-to-head comparison of interferon beta-1b (Betaseron, Bayer HealthCare Pharmaceuticals [erstwhile Berlex]) and glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) shows comparable efficacy but continuing multiple sclerosis (MS) disease activity with both agents.

    The study, called Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints (BECOME), is the first investigator-initiated, randomised, prospective, rater-blinded trial to directly compare these 2 agents in the treatment of MS. The study was supported in part by a grant from Berlex/Schering AG.

    Diego Cadavid, MD, associate professor in the department of neurology and neurosciences, New Jersey Medical School, in Newark, and the Multiple Sclerosis Center at Holy Name Hospital, in Teaneck, New Jersey, reported the findings here during the Whitaker Research Track presentations of the Consortium of Multiple Sclerosis Centers 21st Annual Meeting.

    Seventy-five patients with MS were randomly assigned to treatment groups: 36 with interferon beta-1b and 39 with glatiramer acetate. Combined active lesions (CAL) were monitored monthly for 2 years using 3-tesla MRI with triple-dose gadolinium and a 40-minute delay to maximise enhancement. Clinical indications of relapse, cognition, and disability were also monitored. A total of 2754 CALs were identified during the study.

    After 15 months of treatment, a similar number of lesions occurred in both treatment groups, but the occurrence of lesions varied considerably between patients. "Approximately half the MRIs in each group showed new lesions and half did not," he said.

    Dr. Cadavid then reclassified the 75 patients by CAL pattern: no CALs for 2 years (n=15), episodic CALs (n=44), and frequent CALs (n=16). The occurrence of these patterns in the 2 treatment groups was not significantly different (Χ2, P = .7).

    Disease activity continued to some extent in 77% to 83% of the patients, again with no significant difference between the 2 drug therapies.

    Sensitive Technique

    Michael Racke, MD, chair of the department of neurology of Ohio State University and moderator of this session, focused his comments to Medscape on the unusually sensitive MRI technique. "In terms of clinical applicability, nobody's going to do monthly triple-dose gadolinium 3-tesla MRI. But the real problem is, we don't have a histologic correlate."

    "Dr. Cadavid's data do suggest that the 2 drugs compared are very similar," continued Dr. Racke. However, he thinks the unusual MRI technique used in this study is measuring something different than an MRI with, for instance, a 1.5-tesla magnet after single-dose gadolinium. "Basically, since Berlex funded the study, they thought that Betaseron would beat Copaxone and it didn't. So the issue becomes: Why is that? With a typical MRI, would you have seen what was anticipated? This technique is very sensitive, but we don't know exactly what we're measuring with that increased sensitivity."

    CAL Patterns

    Dr. Cadavid also analysed the results of the behavioural and cognitive tests for the 3 CAL pattern groups, including the 25-foot walk test, a test of response speed, and the cognitive skills index (CSI). In nearly every test, the group with frequent CALs scored lower than other groups in baseline testing and continued to do more poorly throughout the study.

    Talking with Medscape, Dr. Cadavid said he had been very surprised to find that patients in the frequent-CAL group scored more poorly from the beginning of the assessments. As to why their impairment had not been noticed earlier, he commented: "It's a matter of how the relapse presents. If they lost vision in 1 eye, they'd be picked up right away. But if they have a subtle problem with balance, gait, or cognition, they may not be picked up. People tend to assign the symptoms to something else."

    Regarding clinical utility of the 3 CAL patterns, Dr. Cadavid emphasised: "You cannot assume that just because you put [patients] on therapy you've got them under control. You have to be careful, especially with the group with frequent lesions, because they seem to already carry some loss of function when you first see them." Based on the results of this study, he added, "Even though you put them on the drug, you are not really controlling them. They're getting disabled in front of you."

    The point is, he added, "after 10 or 12 years of these first-level drugs, we are entering a phase of what seem to be more powerful drugs with more serious side effects. We cannot put everybody in the same basket. It's time to become more selective and target the patients with more frequent lesions with what may be more powerful drugs with a higher risk."

    Source: Consortium of Multiple Sclerosis Centers 21st Annual Meeting. John Whitaker Research Track. (16/06/07)

    Super-Early MS Treatment Best
    Treat a disease even before it's diagnosed? Yes, if the disease is multiple sclerosis, new research shows.

    An MS diagnosis is complex and often depends on more than one attack of neurological symptoms such as limb weakness or blurred vision. Doctors tend to take up to a year to make the diagnosis, and only then make treatment decisions.

    Now a new study shows that it's not enough to treat multiple sclerosis as soon as it's diagnosed. The time to start treatment is when you've had a single MS-like event, says Mark S. Freedman, MD, FRCPC, director of the MS research center at the University of Ottawa in Ontario, Canada.

    "The first paradigm shift came at the end of the 1990s, when we learned that waiting for an MS relapse is too late, and we started treating MS at the time of diagnosis," Freedman tells WebMD. "Now we see you have to start when you think you have MS. This is the new paradigm shift in MS treatment."

    That "startling" conclusion comes from compelling data Freedman reported today at the Consortium of Multiple Sclerosis Centers annual meeting in Washington. Freedman also reported some of the data at last month's meeting of the American Academy of Neurology in Boston.

    Freedman and colleagues at 98 MS treatment centers in 20 nations studied 468 patients who had a first episode of what doctors call "clinically isolated syndrome" suggestive of MS. Half were treated right away with Betaseron, one of three beta-interferon drugs currently approved for MS treatment. The other half got inactive placebo injections and only got the real drug when their MS diagnosis was confirmed.

    After just three years, Freedman says, 85% of the patients initially treated with placebo showed signs of "sustained progression" to full-blown MS -- even though most of them had already switched to Betaseron a year or more earlier. Only 15% of the patients given immediate treatment had sustained progression.

    "Permanent damage happens very early in MS, much earlier than we had anticipated," Freedman says. "That year to year-and-a-half delay in treatment translates into an accumulation of disability. It was startling to see that at just year three of the study."

    Rx: Super-Early MS Treatment

    This means a sea change in MS treatment, says Robert Fox, MD, medical director of Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research.

    "We have finally shown that treating MS super early can have a significant impact on the development of disability, which is what patients are most worried about," Fox tells WebMD.

    "This isn't just early treatment -- early treatment is when a patient has had a second episode. Early treatment now turns out to be late," Fox says. "This is the first study to show we need to treat super early, after only a single attack with the diagnosis of MS not confirmed."

    Betaseron is given to patients every other day via injection under the skin. The side effects are flu-like symptoms, which tend to subside after a patient becomes accustomed to the drug.

    Rebif is another beta-interferon given by subcutaneous injection. Avonex is a form of beta-interferon given by once-weekly muscle injections. Fox says he thinks these treatments should work as well as Betaseron, but this has yet to be demonstrated in clinical trials.

    While the new findings are good news for people who get MS in the future, they are sobering news for patients whose treatment started later in the course of their disease.

    "The damage continues to fester two to three years later despite the fact that patients are on beta-interferon," Freedman says. "Even the delayed treatment is effective -- but you don't regain what you lost."

    Late Treatment Still Effective

    Don't tell Amelia Davis that late treatment doesn't help. Davis, now 38, was diagnosed with remitting/relapsing MS two months before her 30th birthday, after he woke to find the left side of her body had gone numb from head to toe.

    It was not an early diagnosis.

    "In my 20s, I went completely blind in my left eye," Davis tells WebMD. "That lasted four weeks, and then my sight came back. I was in college, pulling all-nighters, so I thought it was just the stress and the eye strain."

    Four years later, the same thing happened again. Again she wrote it off to working too hard. A few years later, she lost the feeling in both hands for awhile. But she never sought help until half her body went numb.

    At the University of California, San Francisco, doctors quickly diagnosed Davis's MS and put her on Betaseron. In the eight years since, she's never had another MS attack.

    "Whatever damage was done to me is irreversible," Davis acknowledges. "The great news is, on the outside I am not disabled looking. Because I have been on this drug for so long and am still in remission, I think I am going to stay in this remission stage for the rest of my life."

    Davis has advice for other people with MS.

    "If you get on aggressive drug therapy early, it is really proven to slow the disease down. It can stop a major MS episode from happening, where the body cannot repair itself," she says.

    Davis is now a successful photographer. In 2004, she published her second book, My Story: A Photographic Essay on Life with Multiple Sclerosis. Davis also serves as president of MSFriends, a 24-hour multiple sclerosis hotline. Betaseron maker Bayer is the main sponsor of MSFriends.

    Source: CBS News/WebMD © MMVII, CBS Interactive Inc. All Rights Reserved.(04/06/07)

    Early Interferon Beta-1B (BetaseronR) In Multiple Sclerosis Patients Staves Off Disability
    Prompt initiation of interferon beta-1b (Betaseron®) at the onset of suspected multiple sclerosis (MS) translates into less progression to chronic neurologic disability compared with delayed treatment, researchers announced at the 59th Annual Meeting of the American Academy of Neurology (AAN).

    Mark S. Freedman, MD, Director of the Multiple Sclerosis Research Unit at University of Ottawa in Ottawa, Canada, reported that prompt initiation of interferon beta-1b treatment in patients with a first event suggestive of MS was associated with a significant 40 percent reduced likelihood of chronic neurological impairment as measured by the Expanded Disability Status Scale (EDSS) over three years. The EDSS is an established scale for quantifying disability in MS.

    "Some patients already have evidence of significant neurological damage when they initially present with MS, which may set the stage for significant disability later on," Dr. Freedman, who is also professor of neurology, observed. "We have shown for the first time that immediate treatment after a first clinical demyelinating event suggestive of MS can reduce the early neurological damage, which may ultimately delay the development of the debilitating sequelae that characterise advanced MS."

    The results are from a follow-up of patients enrolled in the Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) trial. The study is the first prospective, placebo-controlled, multi-center investigation to test the impact of randomly assigned early versus delayed initiation of interferon beta therapy at the time of a clinically isolated syndrome (CIS) on further evolution of MS.

    Overall, 468 patients with a first clinically demyelinating event suggestive of MS and typical magnetic resonance imaging (MRI) were treated with interferon beta-1b 250 mcg or placebo subcutaneously every other day until either a diagnosis of clinically definite MS was established or they reached two years of evaluation. At this time-point, they were eligible to enter an open-label, follow-up study and were offered interferon beta-1b for up to five years after the start of double-blind treatment.

    At three-year follow-up, patients who initiated interferon beta-1b treatment early were 41 percent less likely to progress to clinically definite MS than patients who delayed the start of treatment.

    "Formerly, I wasn't convinced of the absolute need for starting treatment immediately following the first attack in the majority of patients," Dr. Freedman said. "Like many physicians, I preferred to wait until patients met diagnostic criteria for MS before starting therapy."

    He added: "Based on these data, there is no longer a rationale for withholding therapy, especially given the long-established safety record of a drug like interferon beta-1b."

    Source: Medical News Today Copyright: Medical News Today

    Large Study Shows That Presence of Neutralizing Antibodies Did Not Predict Clinical Response to Betaseron Treatment
    Berlex, Inc., a U.S. affiliate of Bayer Schering Pharma AG, Germany, announced today the results of a retrospective study demonstrating that the presence of neutralizing antibodies (NAbs) that can develop in response to Betaseron(R) (interferon beta-1b) therapy did not predict clinical response in patients with multiple sclerosis (MS). (1) The study looked at data from over 6,600 patients across three continents. It is the largest dataset ever analysed on the relevance of NAbs to interferon beta therapy. The results were published in the March issue of The Journal of International Medical Research.

    "This study confirms that NAbs, which develop in response to Betaseron therapy, tend to disappear over time and provides important evidence that the presence of NAbs in these patient populations was not associated with a poor clinical response to treatment." said Dr. Douglas Goodin, lead author of the article and Professor of Neurology, University of California, San Francisco. "While it is unclear how these findings might apply to other beta interferon therapies, these data underscore the fact that decisions regarding Betaseron treatment should be based on the clinical circumstances of the individual patient and not solely on the basis of their NAb status."

    NAbs are antibodies that may attach themselves to an injected protein drug, such as beta interferon therapy, thereby potentially inhibiting its biological activity. All immunomodulating therapies for MS may cause the development of NAbs in a varying portion of patients, but there is controversy in the medical community about the role NAbs may or may not play in a patient's response to therapy.

    "This study reinforces expert recommendations that treatment decisions should be based on a patient's overall response to therapy and not on the actual or potential presence of neutralizing antibiodies," said Darlene Jody, M.D., Executive Vice President, Specialised Therapeutics, Bayer Schering Pharma AG, Germany. "When treating MS, especially from the first event, patients and prescribers can continue to rely on the proven efficacy and safety of Betaseron."

    The published study addressed the clinical impact of NAbs to Betaseron therapy in an office-based or "real world" setting. These results are in line with the clinical practice guidelines recently published by the American Academy of Neurology. (2) Since the development of NAbs is specific to each medication, it is unclear how these findings for Betaseron might apply to other beta interferons.

    About the Study

    The study reviewed the NAb status of 6,698 Betaseron patients from North America (n=2010), Europe (n=2417) and Australia (n=2271) using the myxovirus protein A assay (MxA). The prevalence of persistently high neutralizing antibodies in the Australian cohort, which included patients regardless of clinical response to Betaseron, was 37%. This finding was similar to the reported incidence seen in Betaseron clinical trials. The incidence of persistently high NAbs in the European and North American groups, however, was only 28% and 21% respectively even those these patients were pre-classified as having a "poor clinical response" to therapy. Since the patients known to be poor responders were more often NAb negative than the general population, the study concluded that persistent, high NAb status was not a key predictor of clinical response to therapy.

    Data for the study were collected during a six-year period (1996-2002). Most of the NAb testing (73%) was performed within the first three years of treatment, when patients are thought to be at the greatest risk of developing NAbs. Patients in the study had MS for an average seven to 10 years at the time of testing.

    (1) Goodin, DS, Hurwitz B, Noronha A.. Neutralizing Antibodies to Interferon beta-1b are Not Associated with Disease Worsening in Multiple Sclerosis. J Int Med Res. 2007; 35: 173-187.

    (2) Goodin DS et al. Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2007; 68: 977-984.

    Source: Red Orbit.com © 2002-2007 redOrbit.com. All rights reserved

    Betaferon(R) Approved in Australia for Earliest Stages of Multiple Sclerosis
    Schering AG, Germany majority-owned by the Bayer Group, announced today that the Australian Therapeutic Goods Administration has expanded the indication of Betaferon(R) (interferon beta-1b) to include patients with a first clinical event suggestive of multiple sclerosis (MS). This approval provides an important treatment option for patients in Australia to reduce the risk of developing clinically definite MS (CDMS), and thus creates the potential to delay the progression of the disease.

    Earlier this year, Betaferon was granted marketing authorisation in Europe, the United States and Canada for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

    "We are pleased that Betaferon is now available also for treatment of early MS in Australia where it is already the most prescribed MS treatment. With this approval, physicians and patients have a trusted treatment option for the early stages of the disease, when it has the greatest impact," said Dr. Darlene Jody, Head of Specialized Therapeutics at Schering Group.

    The label extension is based on results from the BENEFIT study which showed that Betaferon 250 mcg treatment in the early phase of the disease reduced the risk of developing CDMS by 50 percent compared with placebo. Furthermore, patients in the Betaferon group were two times better protected than placebo-treated patients against developing MS as defined by the McDonald diagnostic criteria. Betaferon was also very well accepted in the BENEFIT study, with 93 percent of patients completing the two-year study period.

    Source: PRNewswire Copyright © 2006 PR Newswire. All rights reserved.

    Schering Says FDA Approves Additional Use Of Multiple Sclerosis Drug Betaseron
    Berlex Inc., a U.S. affiliate of Schering AG, Germany, on Monday said the U.S. Food and Drug Administration has expanded the indication of Betaseron to include patients with multiple sclerosis or MS who have experienced a first clinical episode and have MRI features consistent with MS.

    The company said Betaseron is the only high-dose, high-frequency interferon beta indicated for patients at the earliest stage of MS. It is already indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations.

    A two-year study known as BEtaseron in Newly Emerging multiple sclerosis for Initial Treatment or BENEFIT showed that that treatment with Betaseron delayed the time to a second clinical event by one year compared to placebo. The study, conducted in 468 participants, also showed that treatment with Betaseron reduced the risk of progression to clinically definite MS by about 50% and to MRI-defined MS by 46% compared to placebo.

    The results of the BENEFIT trial also showed that the patients were willing to initiate and continue Betaseron treatment in an effort to gain control of the disease at its earliest stages.

    Source: Trading Markets.com Copyright(c) 2006 RealTimeTraders.com, Inc. All Rights Reserved

    First Patient Enrolled in Study to Evaluate Impact of Regular Neutralizing Antibody (NAb) Testing on Multiple Sclerosis Treatment Patterns
    Largest Study of Its Kind Will Examine Changes in Treatment Management of Tested and Non-Tested Patients Receiving a High-Dose Interferon.

    Teva Neuroscience, Inc., announced today the initiation of the first-ever study designed to examine how the implementation of regularly scheduled interferon beta  (IFN-(beta) ) neutralizing antibody (NAb) tests in multiple sclerosis (MS) patients receiving high-dose IFN-(beta) therapy ultimately affects treatment patterns, versus the usual care of IFN-(beta) patients. The study, called the NAbs Count Study, began enrollment in approximately 130 centers across the United States with the first patient entering the trial on July 25, 2006.

    Studies have shown that the presence of IFN-(beta) NAbs may negatively alter the therapeutic effectiveness of the commercially available IFN-(beta) class of disease modifying drugs commonly used to treat multiple sclerosis, which includes IFN-(beta)-1a SC (Rebif®), IFN-(beta)-1b SC (Betaseron®), and IFN-(beta)-1a IM (Avonex®), and that NAbs developed in five percent to 45 percent of all multiple sclerosis patients treated with these drugs (1, 2, 3). Despite the evidence that patients who develop NAbs are likely to become IFN-(beta) non-responders, and present an increased risk of relapses and disease progression, NAbs testing has not been a part of routine clinical practice (4).

    "The initiation of the NAbs Count Study underscores Teva's long-standing commitment to the MS community," said Judy Abdalla, Senior Director Medical Affairs, Teva Neuroscience. "We are excited to be working with some of the top medical centers in the United States to gather information that could provide additional information on what guides multiple sclerosis treatment decisions."

    The European Federation of Neurological Societies (EFNS) released guidelines recommending that IFN-(beta) NAbs testing be conducted in all IFN-(beta)-treated MS patients at 12 and 24 months of therapy. The EFNS guidelines also recommend that testing should be repeated in patients who test positive for NAbs and therapy with IFN-(beta) should be discontinued in patients with high titers of NAbs sustained at repeated measurements with 3- to 6-month intervals (5).

    About the Study

    The NAbs Count Study is a 12-month, randomised, controlled, open-label, parallel group study taking place in approximately 130 study sites in the United States. Patients 18 years of age and older with a diagnosis of MS who have been receiving high-dose IFN-(beta) therapy at approved doses - either Rebif® or Betaseron® - continuously for at least 12 months are eligible. The study is expected to enroll approximately 2,440 subjects.

    Patients will be randomised to one of two study groups. One group of patients (Regularly Scheduled NAb Testing Arm) will be scheduled for multiple IFN-(beta) NAb tests (up to 3 NAb tests over a nine-month period) with a follow-up visit at 12 months. The other cohort of patients (Usual Care Arm) will be observed for 12 months under usual care conditions, which typically do not include regularly scheduled NAb tests. As the primary endpoint of the study, researchers will evaluate the differences between study arms in the proportion of subjects whose high-dose IFN-(beta) therapy was changed during a 12-month follow-up period. Patients and health care providers interested in learning more about the study can visit www.clinicaltrials.gov and enter the trial's identifier code of NCT00336557 for more information.

    Please see enclosed additional important information.

    (1)Avonex® Prescribing Information, www.avonex.com (2)Rebif® Prescribing Information, www.rebif.com (3)Betaseron ® Prescribing Information, www.betaseron.com (4)Giovannoni G, Goodman A. Neutralizing anti-IFN-{beta} antibodies: How much more evidence do we need to use them in practice? Neurology 2005; 65(1):6-8.

    (5)P.S. Sorensen, et al. "Guidelines on use of anti-IFN-(beta) antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-(beta) antibodies in multiple sclerosis" European Journal of Neurology 2005, 12: 817-827

    Source: Teva Neuroscience, Inc.

    Trial Results Published in Neurology Show Risk of Developing Multiple Sclerosis Significantly Reduced with Interferon Beta-1b Early Treatment
    Researchers have found that treatment of patients with interferon beta-1b after a first attack suggestive of multiple sclerosis (MS) cuts their risk of developing the disease in half over the next two years, according to results from the BENEFIT (BEtaferon®/BEtaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) clinical trial. The findings were published for the first time in an expedited manner in this week's online issue of Neurology.

    One of the primary investigators of the BENEFIT study was Mark S. Freedman, MSc MD FAAN FRCPC, of The Ottawa Hospital and the University of Ottawa in Ottawa, Canada. Ottawa was one of 93 test sites in 20 countries where this 487 patient, double-blinded, phase III study was conducted.

    "Our study provides a strong rationale for the early use of early interferon beta-1b therapy after the first episode suggestive of MS," said Dr. Freedman. "It is well established that neurological damage, including damage of the nerve fibers or axons, can occur even before MS is diagnosed. The current thinking is that by limiting the amount of axonal damage through early and effective therapy, we can postpone a person's disability. The prime concern of people with MS is that they will become disabled in the next 10 to 20 years."

    Dr. Freedman continued, "It is important for people who are experiencing symptoms of MS to see a neurologist for diagnosis and treatment. The findings of the BENEFIT study show that early treatment with interferon beta-1b helps to reduce the risk of developing MS."

    The two-year data published in Neurology show that treatment with interferon beta-1b, at really the earliest clinically identifiable time point in the evolution phase of the disease, reduced the risk of developing clinically definite MS by 50 percent, compared with patients who received a placebo drug. BENEFIT is the only early two-year MS trial that utilised a high dose, high frequency interferon-beta therapy, which has already been shown to be superior to low dose/frequency regimens in patients with established relapsing-remitting disease.

    In the BENEFIT study, over 85 percent of those patients who did not receive the therapy but were on a placebo-drug, went on to meet current diagnostic criteria for MS by either developing new MRI lesions or experiencing another clinical attack within two years of having their first clinical event. In contrast, patients who received the interferon beta-1b therapy were two times better protected against developing MS.

    The BENEFIT study was supported by funding from Schering AG, Germany, marketers of BEtaferon BEtaseron ®/ ®.

    Source: The Ottawa Hospital

    Schering Receives Canadian Approval for Betaferon as Treatment for Early Stage Multiple Sclerosis
    Betaferon® (interferon beta-1b), a drug against multiple sclerosis (MS) developed by Schering, AG, has been granted marketing authorisation by Canadian regulators for an extension of its indication to include the treatment of patients with a first clinical event suggestive of MS. The drug is marketed as Betaseron® in Canada by Schering's affiliate Berlex Canada Inc.

    With this approval, Betaferon becomes the highest-dose highest-frequency therapy approved for the treatment of the earliest stages of MS in Canada. The approval provides an important treatment option for patients to reduce the risk of developing clinically definite MS (CDMS), and the potential to delay the progression of the disease.

    A similar supplemental biologics license application (sBLA) has also been applied to the US FDA in February, and is awaiting approval.

    Source: Schering

    New Autoinjection Device Designed to Work With Betaseron(R) Now Available For Patients With Multiple Sclerosis
    Betaject(R)3 Offers Convenient Delivery Option.

    Berlex, Inc. today announced the availability of Betaject® 3, a new autoinjection device specifically designed to work with Betaseron® (interferon beta-1b) as an optional injection method for patients with relapsing forms of multiple sclerosis (MS). The Betaject 3 autoinjection device is an easy-to-use, mechanical device that automatically delivers subcutaneous injections and may help make it easier for patients to inject their medication.

    "With Betaject 3, we've simplified the process for patients by eliminating an entire set-up step prior to each injection," said Dr. Ludger Heeck, Vice President and General Manager of Specialized Therapeutics at Berlex. "It complements the convenient, refrigeration free-formulation Betaseron offers, and provides patients with an optional tool to help make using Betaseron therapy quick and easy."

    Ease of Use, Convenience and Support

    The Betaject 3 autoinjection device is the latest innovation designed to assist patients on Betaseron treatment. Eliminating a calibration step prior to each injection, this optional injection device automatically delivers subcutaneous injections of Betaseron at a standard preset needle depth, allowing patients to more easily self-inject their medication than with devices that require calibration.

    Betaseron is the only available refrigeration-free MS therapy that can be stored at room temperature for longer than 30 days(1). This unique product attribute simplifies the injection process by eliminating waiting time and allows patients more options for traveling with and storing their medication in a discrete, safe manner.

    Along with the availability of products designed to help simplify the treatment process, Berlex offers personal support programs for people using Betaseron through its MS Pathways and B.E.T.A. Nurse programs. The B.E.T.A. Nurses assist people with MS beginning therapy with Betaseron by providing in- person injection training. B.E.T.A. Nurses maintain ongoing communication throughout the course of therapy to help them and their caregivers adjust to treatment and ease some of the challenges often associated with the disease. Research has shown that Betaseron patients who participated in the B.E.T.A. Nurse program were more likely to maintain their course of therapy with nearly 90 percent of people in the program remaining on treatment after one year.

    For more information about the optional Betaject 3 autoinjection device, Betaseron or the B.E.T.A. Nurse program is available by calling MS Pathways at 1.800.788.7467 (US and Canada Only).

    About Betaseron

    Betaseron® is approved for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Treatment with Betaseron has been shown to sustain reduction in the annual rate of relapses of up to 40 percent over 16 years. Patients remaining on long-term(2) Betaseron treatment have shown slower disease progression, nearly doubling the time it took to reach confirmed EDSS 6(3).

    Approved in 1993 as the first disease-modifying therapy for the treatment of MS, Betaseron has more than 16 years of clinical experience, with a well- established safety profile resulting from more than 600,000 patient years of treatment. The 16-Year Long-Term Follow-up Study is the longest follow-up study for any disease-modifying therapy in MS, demonstrating that Betaseron remains consistently safe, effective and well tolerated over the long term. Berlex remains committed to its clinical study program, which continues to generate data that reinforce the role of Betaseron as a groundbreaking first- line therapy for the treatment of relapsing MS patients.

    The most commonly reported adverse reactions associated with Betaseron treatment are lymphopenia, injection site reaction, asthenia, flu-like symptom complex, headache, and pain. Betaseron should be used with caution in patients with depression. Injection site necrosis has been reported in five percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. Please see full Prescribing Information available at http://www.betaseron.com

    About Berlex

    Berlex, a U.S. affiliate of Schering AG, Germany, is committed to addressing unmet medical needs through research and development in the areas of oncology, gastroenterology, women's health, diagnostics and neurology. Berlex also markets diagnostic imaging agents, innovative treatments in the areas of female health care and oncology, as well as specialised therapeutics for life-threatening and disabling diseases of the central nervous system and cardiovascular system. Berlex has business operations in New Jersey, California and Washington states. For more information, please visit http://www.berlex.com

    Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex's plans and objectives to differ materially from those expressed or implied in the forward-looking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

    (1) Betaseron is the only immunomodulatory therapy that can be stored at room temperature for greater than 30 days. After reconstitution, if not used immediately, the product should be refrigerated and used within 3 hours.

    (2) Results from the Betaseron 16-Year Long-Term Follow-up Study presented at the 58th Annual Meeting of the American Academy of Neurology. Among the patients who reached EDSS(*1) level 6.0 (e.g., needing a cane for walking), those on long-term Betaseron treatment reached EDSS 6.0 after a median time of 13 years compared to seven years for patients on short-term treatment. Long-term treatment was defined as use of Betaseron for more than 80 percent of the time since the start of the pivotal trial (approx. 12 years or longer), while short-term treatment was defined as use for less than 10 percent of the time (approx. 1.6 years or less).

    (3) EDSS or Expanded Disability Status Scale is a standard method of evaluating a person's level of impairment due to MS. EDSS level of 6.0 is defined as being able to walk, but needing a cane, crutch or brace for assistance.

    Source: Berlex, Inc.

    Schering says MS drug Betaferon approved in EU for early-stage treatment
    Schering AG said its multiple sclerosis drug Betaferon has been approved in Europe as a first-line treatment for the earliest stages of multiple sclerosis.

    The approval is valid in all 25 European member states as well as in Iceland and Norway.

    Schering said this new label allows for the treatment of the majority of patients at risk of getting multiple sclerosis, and includes patients who have signs only suggestive of MS.

    Schering said the 'approval provides an important treatment option for patients to reduce the risk of developing clinically definite MS (CDMS), and the chance to delay the progression of the disease'.

    The approval is based on the BENEFIT study, which showed that Betaferon treatment in the early phase of the disease reduced the risk of developing clinically definite MS by 50 percent compared to placebo.

    'The results of the BENEFIT trial show that Betaferon can substantially slow down the course of MS in early patients, especially those at the earliest stage of the disease, when it has the greatest impact", said Darlene Jody, head of specialized therapeutics at Schering.

    The drug, marketed under the name Betaseron in the US, is currently also under review for use in early stage MS there, and the Food and Drug Administration is expected to make a decision on approval later this year.

    Betaferon was first approved by the EU in 1995.

    This year, Schering is targeting high single-digit sales growth for the drug.

    Source: AFX News Copyright AFX News Limited 2005. All rights reserved.

    Schering receives recommendation for early use of Betaferon in MS from EU body

    Schering AG said it has received a recommendation from the EU committee for medicinal products (CHMP) that use of Betaferon in early-stage multiple sclerosis patients be approved by the European Commission.

    The Committee's decision is based on the BENEFIT study, which showed that Betaferon treatment in the early phase of the disease reduced the risk of developing clinically definite MS (CDMS) by 50 percent compared to placebo.

    A decision by the Commission is expected by this summer.

    Sixteen-Year Follow-up Study Reinforces Betaseron(R) Long-Term Efficacy, Safety and Tolerability in Multiple Sclerosis
    Efficacy in relapse rate reduction beyond five years shown for the first time

    Berlex announced today that Betaseron® (interferon beta 1b) remained consistently safe, effective and well tolerated over the long term, according to results of the Betaseron 16-Year Long-Term Follow-up (16-Year LTF) Study presented at the 58th Annual Meeting of the American Academy of Neurology. This is the longest follow-up study for any disease modifying therapy in multiple sclerosis (MS).

    Patients with relapsing forms of MS taking Betaseron (known as Betaferon® outside the US) had a sustained reduction in the annual rate of relapses of up to 40 percent over 16 years.

    The data also showed that patients remaining on long-term Betaseron treatment had a slower disease progression compared to patients who did not. Among the patients who reached EDSS(1) level 6.0 (e.g., needing a cane for walking), those on long-term Betaseron treatment reached EDSS 6.0 after a median time of 13 years compared to seven years for patients on short-term treatment. Long-term treatment was defined as use of Betaseron for more than 80 percent of the time since the start of the pivotal trial (approx. 12 years or longer), while short-term treatment was defined as use for less than 10 percent of the time (approx. 1.6 years or less). The impact of long-term treatment on disease progression is being studied further using historical control groups.

    "This study has comprehensively re-evaluated patients after 16 years," said Professor George Ebers, lead investigator of the study, Department of Clinical Neurology, Radcliffe Infirmary, University of Oxford. "The evidence for relapse rate reduction, combined with further support for long-term safety of Betaseron, is convincing. More studies are being done to further analyze the impact of treatment on disease progression."

    The long-term use of Betaseron over 16 years revealed no new or unexpected adverse events. Betaseron was well accepted by patients in this long-term study. The median treatment duration with Betaseron of the analyzed trial participants was almost 10 years, while the longest duration on therapy is 17.1 years.

    "The 16-year LTF is ground-breaking in that it is the longest follow-up study of patients on disease modifying MS therapy," said Richard Neiman, MD, Vice President, Head of Medical Affairs at Berlex. "These results show that first-line and long-term use of Betaseron for relapsing MS patients is safe, effective and well-tolerated. These data are very reassuring given the chronic nature of relapsing forms of MS, and the need for long-term therapy."

    Sixteen Years of Betaseron Use in Patients with MS

    The 16-Year LTF Study provides clinical assessment of patients who first enrolled in the Betaseron pivotal trial between 1988 and 1990. Of the original 372 patients involved in the pivotal trial, 328 (88.2 percent) have been identified. It is a multicenter, open-label, observational study designed to evaluate the impact of Betaseron treatment on long-term outcomes in patients with relapsing forms of MS. The study constitutes the longest follow up for any disease-modifying therapy in MS.

    The results support a previously reported trend, in that there was a lower number of deaths in patients that were initially treated with Betaseron 250 mcg during the pivotal trial. This trend needs to be further evaluated.

    The Betaseron pivotal trial was the first large, randomized, placebo- controlled study of any therapy in MS. This groundbreaking study was conducted in North America and led to the approval of Betaseron, the first disease-modifying agent for MS, in 1993. Patients were randomly assigned to one of three study arms, Betaseron® 50 mcg(2), Betaseron 250 mcg or placebo, with a median duration of observation of 45 months. Analysis after two years demonstrated that significantly more patients receiving Betaseron were relapse-free, that those relapses that occurred were less frequent and that hospitalizations for MS were cut nearly in half. These results were confirmed at five years.

    About Betaseron

    Betaseron® is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. The most commonly reported adverse reactions are lymphopenia, injection site reaction, asthenia, flu-like symptom complex, headache and pain. Betaseron should be used with caution in patients with depression. Injection site necrosis has been reported in 5 percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. Please see full Prescribing Information for more information.

    About Berlex

    Berlex is committed to addressing unmet medical needs through research and development in the areas of oncology, gastroenterology, women's health, diagnostics and neurology. Berlex also markets diagnostic imaging agents, innovative treatments in the areas of female health care and oncology, as well as specialized therapeutics for life-threatening and disabling diseases of the central nervous system and cardiovascular system. Berlex has business operations in New Jersey, California and Washington. For more information, please visit http://www.berlex.com.

    Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex's plans and objectives to differ materially from those expressed or implied in the forward-looking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

    (1) EDSS or Expanded Disability Status Scale is a standard method of evaluating a person's level of impairment due to MS. EDSS level of 6.0 is defined as being able to walk, but needing a cane, crutch or brace for assistance.

    (2) The Betaseron 50 mcg dose was a study dose only. The FDA approved and marketed dose is Betaseron 250 mcg.

    Source: Berlex

    Berlex Files Application for Use of Betaseron in Patients with a First Clinical Episode Suggestive of MS
    Berlex, Inc. announced today that the U.S. Food and Drug Administration (FDA) has accepted the filing of a supplemental biologics license application (sBLA) requesting an expanded label for its multiple sclerosis (MS) therapy, Betaseron® (interferon beta-1b).

    The submission seeks approval for the use of Betaseron to delay a second exacerbation in patients who have experienced a first clinical demyelinating event -- either monofocal (i.e., clinical evidence of a single lesion) or multifocal (i.e., clinical evidence of more than one lesion). Currently, Betaseron is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. The company anticipates a response by Q4 2006.

    Berlex, Inc. is supporting its application for this expanded indication based on data from its randomized study, BENEFIT*, the largest study of patients with the first clinical signs of MS. The BENEFIT trial showed that Betaseron treatment reduced the risk of developing clinically definite MS (CDMS) by 50 percent compared with placebo. Furthermore, patients in the Betaseron group were two times better protected against developing MS as defined by the McDonald diagnostic criteria. Results of the BENEFIT study were presented at the joint ECTRIMS/ACTRIMS Congress on September 30, 2005, in Thessaloniki, Greece.

    "The acceptance of the filing is an important step towards a new and effective treatment option for patients with early MS," said Dr. Ludger Heeck, Vice President and General Manager of Specialized Therapeutics at Berlex.

    * Betaferon®/Betaseron® in Newly Emerging MS For Initial Treatment

    Additional Information

    About Betaseron

    Betaseron® is approved for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. The most commonly reported adverse reactions are lymphopenia, injection site reaction, asthenia, flu-like symptom complex, headache, and pain. Betaseron should be used with caution in patients with depression. Injection site necrosis has been reported in 5 percent of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. Please see full Prescribing Information for more information.

    About Berlex

    Berlex is committed to addressing unmet medical needs through research and development in the areas of oncology, gastroenterology, women's health, diagnostics and neurology. Berlex also markets diagnostic imaging agents, innovative treatments in the areas of female health care and oncology, as well as specialized therapeutics for life-threatening and disabling diseases of the central nervous system and cardiovascular system. Berlex has business operations in New Jersey, California and Washington. For more information, please visit http://www.berlex.com.

    Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex's plans and objectives to differ materially from those expressed or implied in the forward-looking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

    Source: Berlex, Inc.

    Study Shows Treatment With Interferon beta-1b Delays the Development of MS in Patients With First Clinical Signs of the Disease
    Interferon beta-1b 250 mcg(1)
    treatment delayed the onset of clinically definite multiple sclerosis (CDMS)
    by one year (363 days) in patients with first clinical signs of multiple
    sclerosis
    (MS) compared to placebo, according to new findings from the BENEFIT (Betaferon/Betaseron in Newly Emerging MS For Initial Treatment) study presented at today's joint 21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS), Thessaloniki, Greece, by Professor Ludwig Kappos, Professor of Neurology and Clinical Neuroimmunology at the University of Basel, Switzerland.

     The multi-centre, double-blind, randomized, phase III BENEFIT study was conducted in 98 centres in 20 countries and included a total of 487 patients presenting with a single clinical episode suggestive of MS, for a period of up to 24 months. Two primary endpoints were evaluated:

        -  Time to CDMS based on a relapse or EDSS progression 1.5 points

        -  Time to MS according to the criteria by McDonald et al. (2001)

    Results from the study showed that treatment may significantly delay the
    development of CDMS. Patients in the treatment group experienced an additional 363 days delay in development of CDMS compared to the placebo group. At day 255 of the study, one-quarter of patients in the placebo group had developed CDMS, while it took 618 days for a comparable number of patients to develop CDMS in the treatment group. At the end of the two-year period, 45 percent of the placebo group compared with 28 percent in the interferon beta-1b group  (p less than 0.0001) had developed CDMS, a relative risk reduction of 50 percent in the group treated with interferon beta-1b.

    "Treatment with interferon beta-1b appears to delay patient progression
    to CDMS when they have been identified as being at risk of developing the
    disease," said Ludwig Kappos, Professor of Neurology and Clinical
    Neuroimmunology at the University of Basel, Switzerland and lead investigator of the BENEFIT study.

    "The BENEFIT study was rigorously controlled and will lend support to making early treatment decisions in patients with the first clinical signs of MS."

    In assessing MS progression against the McDonald criteria, patients in
    the interferon beta-1b group were two times less likely to develop MS: fifty- one percent of the placebo group had already progressed to MS after six months, and 85 percent within two years compared with 28 percent and  
    69 percent of the interferon beta-1b treated group, respectively (p less than
    0.00001).

    The study also demonstrated that people who have symptoms suggestive of
    MS are willing to accept and comply with this treatment regimen that asks for
    every other day subcutaneous (s.c.) injections. Ninety-four percent and      
    93 percent of the placebo and interferon beta-1b patients, respectively,
    completed the two-year study period. Additionally, 95 percent of all eligible
    patients chose to enter the BENEFIT follow-up study taking open-label
    interferon beta-1b every other day treatment. The high patient acceptance to therapy in the study was facilitated through the implementation of a series of steps designed to improve a patient's tolerability to therapy, including a
    dose titration regimen at the initiation of therapy, the use of auto-injectors
    and co-medication with an analgesic.

    About BENEFIT

    The BENEFIT study is the first randomized multi-centre study designed to
    explore the impact of a high-dose, high-frequency beta interferon therapy on the progression of disease in patients with first clinical signs of MS.

    A randomised, double blind, placebo controlled, parallel-group, multi-
    centre clinical trial, the BENEFIT study was carried out among 487 patients
    presenting with the first clinical event suggestive of MS within the last 60
    days. These patients presented with either "monofocal" (clinical symptoms
    explained by one single CNS lesion) or "multifocal" (clinical symptoms
    explained by at least two underlying CNS lesions) symptoms and with a magnetic resonance imaging (MRI) screening scan suggestive of MS. Patients were randomized to one of two groups receiving interferon beta-1b 250 mcg or placebo s.c. every other day for up to 24 months continuously. All study participants completing the double blind study were then invited to
    participate in a separate open-label follow-up study with interferon beta-1b.

    The open label study will prospectively assess the impact of early treatment
    as compared to delayed treatment with interferon beta-1b on the long-term
    course of the disease for a total observation time of five years, as well as
    on the formation of new brain lesions as measured by MRI.

    (1) Interferon beta-1b is marketed by Schering AG as Betaferon in Europe and by Berlex Laboratories as Betaseron in the U.S. and Canada. In the US, Europe and Japan, interferon beta-1b has been approved for all
    relapsing forms of MS. It is given on alternate days as a subcutaneous
     injection of 250 mcg.

    The BENEFIT (Betaferon/Betaseron in Newly Emerging MS For Initial Treatment) study is sponsored by Schering AG Germany.

    Source: Schering AG Germany

    MS interferon therapy at a crossroads

    More evidence shows neutralizing antibodies hamper effect of treatment

    Should Canadian neurologists be testing their multiple sclerosis patients on interferon beta-1a or interferon beta-1b therapy for neutralizing antibodies? And if a patient tests positive, what then?

    The questions have been brought up again by an editorial and three papers in a recent issue of Neurology.

    Previous studies suggested the presence of neutralizing antibodies affected clinical outcomes and markers of disease progression seen with imaging, but the full implications of how they affect interferon therapy in MS was not clear. Neutralizing antibodies against interferon beta typically appear after six to 24 months of interferon treatment, so their impact on outcomes could not be properly assessed with some of the earlier, shorter trials.

    The papers in Neurology provide more evidence that neutralizing antibodies interfere with clinical outcomes and show that if a patient repeatedly tests positive, the antibodies are bound to stay.

    A two-year extension of the PRISMS (prevention of relapses and disability by interferon beta-1a subcutaneously in multiple sclerosis) trial allowed investigators to better examine the issue of neutralizing antibodies. In their report in Neurology, the investigators conclude relapses increased after patients developed neutralizing antibodies to the interferon beta-1a (Rebif). Patients who tested positive for neutralizing antibodies also did more poorly on disability outcome measures compared with those who tested negative.

    A second study, this time from the four-year European interferon beta-1a (Avonex) intramuscular dose comparison study investigators, showed patients with neutralizing antibodies are significantly more likely to have higher relapse rates and worsening of expanded disability status scores from baseline compared with patients who are negative for neutralizing antibodies.

    Results from the Danish Multiple Sclerosis Study group suggest if a patient has not developed neutralizing antibodies after two years of interferon treatment, the chances of them developing them are slim. Patients who remain positive for neutralizing antibodies for more than 18 months will probably remain positive, their findings show.

    The proportion of patients who developed neutralizing antibodies ranged from 3.2% in the European study, to 14% to 22% in PRISMS (with more in the low-dose group) and 40% in the Danish study.

    Canadian neurologists have the means to screen for neutralizing antibodies. All three pharmaceutical companies who manufacture interferon therapies for MS patients offer the test at their laboratories. Physicians must submit a request to have the test done for a specific patient.

    But some say that is not enough. "I think everybody should be tested. That is just my feeling," said Dr. Stanley Hashimoto, a neurologist and clinical professor at the University of British Columbia when asked to comment by the Medical Post. Dr. Hashimoto tests his patients when they come in for routine visits. The cost of the test is covered by the pharmaceutical company.

    Patients have to be tested numerous times because approximately 30% of those who initially test positive for neutralizing antibodies may later spontaneously become negative. This was reflected in the Danish study, which found 7% of the 455 patients treated fluctuated between positive and negative status over the two-year study.

    Dr. Hashimoto said management should be changed if the patients have persistently high titres of neutralizing antibodies.

    "I think that as long as the titres are high and persistent—by persistent I would say between six months to a year—I would stop the drug and wait for the titre to come down to zero," he said.

    There are problems with testing Canadian MS patients for neutralizing antibodies. For one, the laboratory technique that produces the most reliable results has not been established. There are also no standardized cutoff points for "high" and "low" levels of neutralizing antibodies, and what titre is of clinical importance has not been established.

    Then there remains the tricky question: If a patient seems to be doing well on interferon therapy yet tests positive for neutralizing antibodies, what then?

    Dr. Hashimoto said he would stop interferon treatment in patients with persistently high titre of neutralizing antibodies even if the patient was doing well. Interferon beta therapy has a modest benefit, and if the patient is doing well it might not be due to the drug at all.

    "Just because they are doing well certainly is no reason why I wouldn't stop the drug," he said. "Many people disagree with that."

    Guidelines

    In a paper published in the Canadian Journal of Neurological Sciences last year, the Canadian MS working group recommended treatment decisions be made based on clinical observations instead of on levels of neutralizing antibodies.

    "Response to therapy should be weighed on a patient-to-patient basis and take into account the 'little things' we often ignore. If a patient appears to be doing well and objectively we see little change, then that's a good thing. On the other hand, if a patient reports continuing problems, inability to perform their activities of daily living or their job requirements and we find objective change, I would put more weight on those than any neutralizing antibody test," said Dr. Mark Freedman, lead authors of the CJNS paper and director of the multiple sclerosis research unit at the Ottawa Hospital Research Institute.

    "The bottom line is, in very few situations would a neutralizing antibody titre either be helpful or useful in directing the therapy of MS," Dr. Freedman said.

    © Copyright The Medical Post. All rights reserved

    Mitoxantrone and interferon beta-1b regimen shows promise

    Mitoxantrone and interferon beta-1b regimen shows promise

    Pain & Central Nervous System Week via NewsEdge Corporation :

    A regimen of mitoxantrone (MITX) and interferon beta-1b (IFNbeta-1b) shows promise for the treatment of multiple sclerosis (MS).

    Neurologists in the United States conducted a study to "examine the safety of combination therapy" with MITX and IFNbeta-1b) in MS patients with "a high on-therapy relapse rate and enhancing lesions on baseline magnetic resonance imaging (MRI) scan."

    "Ten patients with worsening relapsing-remitting or secondary progressive MS were studied using monthly MRI with triple-dose gadolinium contrast," explained D.R. Jeffery and coauthors at Wake Forest University. "All patients must have been on IFNbeta-1b for at least 6 months, have at least one enhancing lesion on a screening MRI, at least one relapse on IFNbeta-1b in the 6 months prior to study entry and be neutralizing antibody negative."

    "Monthly MRI scans using triple dose contrast and a 30-minute delay between contrast administration and scanning were carried out three times over 2 months to obtain baseline numbers of enhancing lesions each month," the scientists wrote in the journal Multiple Sclerosis. "At the end of the baseline phase, MITX was administered at 12 mg/m2 (month 3), and 5 mg/m2 at months 4 and 5."

    "Dosing was continued at 5 mg/m2 every third month," and "monthly MRI scanning was continued throughout the duration of MITX dosing," according to the report. "The primary outcome measure was the frequency of new enhancing lesions;" secondary outcome measures "included relapse rate, and T1 hypointense and T2 lesion burden."

    "Following the addition of MITX to IFNbeta-1b, mean enhancing lesion frequency decreased 90% at month 7 (p=0.008) and enhancing lesion volume decreased by 96% (p=0.01)," test results revealed. "Relapse rates decreased 64% (p=0.004). T2 lesion burden and T1 hypointense lesion burden increased slightly during the baseline phase and decreased following MITX, but the difference did not reach statistical significance."

    "There were no serious adverse events on combination therapy and no drop-outs due to toxicity," the report stated. "Total white blood cell count was reduced at 14 days post-MITX infusion but returned to normal levels by day 21."

    "There were no neutropenic fevers and there was no clinically significant elevation of liver function tests," published data showed.

    "While the number of patients in this study was small, the results suggest that the combination is safe and well tolerated. Disease activity was substantially reduced following the addition of MITX to IFNbeta-1b," the researchers concluded.

    Jeffery and colleagues published the results of their study in Multiple Sclerosis (A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging. Mult Scler, 2005;11(3):296-301).

    For additional information, contact D.R. Jeffery, Wake Forest University, Bowman Gray School of Medicine, Dept. of Neurology, 300 South Hawthorne Rd., Winston-Salem, NC 27157, USA.

    The publisher of the journal Multiple Sclerosis can be contacted at: Arnold, Hodder Headline PLC, 338 Euston Road, London NW1 3BH, England.

    Keywords: Winston-Salem, North Carolina, United States, Drugs, Interferon Beta-1b, Medical Devices, Mitoxantrone, MRI, Multiple Sclerosis, Neurology, Pharmaceuticals.

    This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. 

    Copyright ©2005 Pain & Central Nervous System Week via NewsRx.com

    Not all Interferon-beta Treatments are Created Equal in Developing Neutralizing Antibodies
    Neutralizing Antibodies can significantly decrease the effectiveness of IFN-b in the treatment of MS

    TORONTO, ONTARIO -- July 14, 2005 -- Three studies published in Neurology which included more than 1200 patients, confirm that the three interferon preparations used to treat relapsing-remitting multiple sclerosis (MS) vary in their rate of production of neutralizing antibodies (NAbs).

    Further, there is agreement that NAbs reduce or eliminate the biologic activity and clinical efficacy of the interferon-beta (IFN-b) therapies.

    Once-weekly Avonex® (interferon beta-1a IM) was shown to be significantly less likely to induce the development of NAbs than the other two available interferon therapies (Rebif® and Betaseron®). Since NAbs reduce or eliminate the clinical benefits of the interferons, these studies highlight a concern for MS patients, neurologists and those who pay for these medications.

    For the many Canadians living with MS, and currently being treated with IFN-b therapy, this is important data.

    "MS is a chronic disease, and patients need to have the confidence that their therapy will retain its efficacy throughout the course of treatment, which is often for many years," commented Dr. Stanley Hashimoto, neurologist and former medical director of the University of British Columbia MS Clinic, Vancouver, Clinical Director of the UBC MS Clinic, Vancouver, British Columbia. "These studies confirm that in MS, high titre and persistent NAbs are very important in eliminating the efficacy of the therapeutic agent. It is important that we have available a less immunogenic option such as Avonex®."

    While each of the studies showed slightly different rates of NAbs, Avonex® (interferon beta-1a IM) consistently demonstrated the lowest rates as compared to the other IFNb therapies. For example, in the first study the Danish Multiple Sclerosis Study group ( Neurology 2005;65:33-39) concluded, "Unlike previous findings reported in the literature we did not find any difference in the proportion of patients treated with [Betaseron®] and [Rebif®] who became NAb-positive, but could confirm that Avonex® is much less immunogenic."

    In the second study, Kappos and associates ( Neurology 2005;65:40-47) analyzed 395 patients over four years in a controlled trial, and clearly demonstrated the loss of efficacy in terms of relapse rate reduction and disability progression over a significant number of years. It can be assumed from this research, that persisting NAbs beyond the four years will continue to suppress the therapeutic activity of the interferons. This was also echoed by Drs. Giovannoni and Goodman in their Editorial (Neurology 2005;65:6-8 ).

    The third study, authored by Dr. Gordon Francis et al. ( Neurology 2005;65:48-55), concluded that, "Neutralizing antibody development in IFN-b-treated patients is correlated with reduced efficacy and is a potential cause for renewed (MS) disease activity."

    "Many patients being treated for MS are not getting the efficacy they deserve because of the neutralizing effect of NAbs," said Dr. Hashimoto "This is not to mention the fact that our healthcare system is paying for these drugs without realizing the potential negative effects of neutralizing antibodies."

    The Danish Multiple Sclerosis study group agreed that the presence of NAbs decrease or eliminate efficacy of the interferons. They recommended that to avoid these negative consequences, all patients on the therapies should be tested at six-month intervals for two years when it becomes less likely the new positivity will develop. Routine testing will assure patients that they are self-injecting their medication and getting benefit from it.

    With recent concerns about existing and future MS treatments, patients and physicians are reassessing currently available therapies, like the interferons. As a result, it is more important than ever to re-evaluate which therapy will provide efficacy over the long-term, including minimizing the formation of NAbs.

    Multiple sclerosis is the most common neurological condition affecting young adults in Canada. MS most often strikes young adults -- women and men between 20 and 40 who are in their most productive family and career years. Women are affected twice as often as men.


    Avonex® is a registered trademark of Biogen Idec Inc.
    Rebif® is a registered trademark of Serono Canada Inc.
    Betaseron® is a registered trademark of Berlex Canada Inc.


    SOURCE: Biogen Idec Inc.

    Interferon Can Reduce Bone Density In Men

    Males treated with interferon were found to have a bone mass density that was lower than that of those who had not been treated with the drug, according to Spanish research.

    Women on interferon had the same bone mass density as those women treated only with corticosteroids.

    Patients with multiple sclerosis are at greater risk of suffering from osteoporosis and pathological fractures, and the use of corticoids together with immobilisation and vitamin D deficiency is one of the causes of low bone mass.

    Results are paradoxical because interferon plays a part in regulating bone metabolism and inhibits the development of osteoclasts, the cells responsible for bone resorption.

    Ref: Rev Neurol 2003 May 16-31;36(10):901-3 Perez Castrillon JL, Cano Del Pozo M, Sanz lzquierdo S, Velayos Jimenez J, Dib Wobakin W. Hospital Rio Hortega, Valladolid, Espa a.

    MS Study Confirms Benefits of High-Dose, High-Frequency Beta Interferon Regiment

    New findings presented at the American Academy of Neurology Annual Meeting in Honolulu, Hawaii revealed clinically relevant differences in disease activity after increasing the dose and frequency of beta interferon therapy in relapsing-remitting MS patients. The results also showed that reducing the dose and frequency of beta interferon is associated with increased disease activity.

    Professor Luca Durelli, Chief of the MS Centre of University Department of Neurosciences, Turin, Italy, and principle investigator of the study, said, "These data confirm the benefits of high-dose, high-frequency beta interferon and demonstrate the risks of changing to a lower-dose regimen even in the absence of clinical or MRI disease activity. These findings will help guide prescribing choices for MS patients."

    Ref: Prof. Luca Durelli - University MS Centre, University of Torino

    Betaseron® May Improve Quality Of Life, Increase Survival Of MS Patients

    Betaseron® May Improve Quality Of Life, Increase Survival Of MS Patients

    Treatment with Betaseron® (interferon beta-1b) appears to improve quality of life and increase survival among patients with relapsing-remitting MS, according to the early results of a long-term study. The original study that led to the 1993 approval of Betaseron® for the treatment of relapsing-remitting MS was conducted between 1988 and 1990. Investigators began contacting the original trial's participants this January to collect data for the follow-up study. To date, 234 of the original patients, or 63 percent, have been identified. Researchers expect to complete the current study, which is the longest follow-up study involving an MS-specific treatment, later in 2005.

    A preliminary review revealed that 39 (50 percent) of the 78 patients treated with Betaseron® in the original trial were more likely to report the continued ability to walk unaided or using aids, as compared with 32 (41 percent) of the 78 patients originally treated with placebo. In addition, 73 of the 78 patients originally treated with Betaseron® are alive while 64 of the 78 patients in the original placebo group are still living. George Ebers, lead investigator of the long-term study, noted that MS generally does not substantially reduce life expectancy, but studies have shown a "modest, yet clear, reduction in untreated patients." "Since MS is a chronic condition that requires life-long treatment, information about long-term experience is the only way that physicians and patients can feel truly confident in long-term efficacy and safety," said Dr. Joachim-Friedrich Kapp, head of specialized therapeutics for the Schering Group. "We are also convinced that MS as a multifaceted disease requires intensive research to investigate and support the importance of initiating treatment as early as possible."

    The company also recently issued a letter reminding health care professionals of the increased risk for hepatic toxicity among patients taking Betaseron®. The company said it is important that patients receive liver function testing at specified intervals following initiation of Betaseron® therapy, even if no symptoms of liver damage are present. Results of the preliminary study were presented at a recent meeting of the American Academy of Neurology. Betaseron® was developed jointly by Chiron Corp. and Berlex Inc. Berlex Inc. is a subsidiary of Schering AG. (27/04/05)

    © Multiple Sclerosis Resource Centre

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