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    You are here : Home » MS Research News » Drugs » Rebif®

    Rebif®

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    FDA approves Rebif Rebidose interferon beta-1a for Multiple Sclerosis

    RebidoseMerck Serono, a division of Germany's Merck, announced that the U.S. Food and Drug Administration (FDA) approved Rebif(R) Rebidose(R) (interferon beta-1a), a single-use auto-injector for the self-administration of Rebif, a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS).

    Rebif Rebidose was evaluated in a 12-week Phase IIIb multicenter, open-label, single-arm study for the self-administration of Rebif with respect to ease of use, patient satisfaction and acceptability, and functional reliability. In the trial, patients with relapsing MS, who were receiving Rebif 44 microgram three times weekly for more than 12 weeks, continued MS therapy using Rebif Rebidose for 12 weeks. The results of the trial showed that the majority of patients found the device easy to use.

    Rebif RebiDose was designed with the objective to assist with ease of use and to offer patients an alternative delivery option. In the US, it will be available in a monthly pack in two different doses, 22 micrograms and 44 micrograms, and in a titration pack.

    Rebif RebiDose was launched in Europe in 2010 and it will be available in the U.S. in early 2013. With this approval, all three delivery options of Rebif (prefilled syringes, Rebiject II and Rebif RebiDose) will be available in the U.S. to provide a range of options to meet the needs of patients treating their relapsing forms of MS with Rebif.

    "Over the past two decades, treatment of relapsing MS has advanced substantially, and Rebif has remained an established treatment option," said Belen Garijo, Head of Global Operations at Merck Serono. "We are committed to invest in valuable incremental innovations developed to bring additional value for the patient."

    Source: Science 2.0 © 2013 ION Publications LLC (04/01/13)

    In MS treated with interferon beta, early disease activity predicts poor outcome

    BetaferonAfter 15 years of follow-up, patients with relapsing-remitting multiple sclerosis (RRMS) who display disease activity despite treatment with interferon (IFN)β-1a tend to have unfavorable long-term outcomes, according to research published online Sept. 13 in the Annals of Neurology.

    Robert A. Bermel, M.D., of the Cleveland Clinic, and colleagues conducted a multicenter, observational, 15-year follow-up study involving 136 patients with RRMS, who had initially been treated with either intramuscular (IM) IFNβ-1a or placebo, to identify early predictors of long-term outcomes.

    The researchers found that significantly fewer patients treated with IM IFNβ-1a had early disease activity. Of those treated with IFNβ-1a, persistent disease activity was associated with an 8.96-fold higher risk of gadolinium-enhancing lesions, a 4.44-fold higher risk of relapse, and a 2.90-fold higher risk of new T2 lesions. Conversely, early disease activity in placebo-treated patients was not associated with long-term outcomes.

    "Disease activity despite treatment with IFNβ is associated with unfavourable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later," the authors write. "The results provide rationale for monitoring IFNβ treated patients with magnetic resonance imaging, and for changing therapy in patients with active disease."

    This study was supported by Biogen Idec.

    Abstract

    Objective:
    To identify early predictors of long-term outcomes in patients with RRMS treated with IM interferon beta-1a (IM IFNβ-1a).

    Methods:
    Multi-center, observational, 15-year follow-up study of patients who completed =2 years in the pivotal trial of IM IFNß-1a for RRMS. 136 patients participated in the 15-year follow-up (69 originally randomized to IM IFNβ-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: 2 or more gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 MRI; 3 or more new T2 lesions on year 2 MRI compared to baseline; and 2 or more relapses over two years. Odds ratios were calculated for early disease activity predicting severe EDSS worsening (worst quartile of change, > 4.5 EDSS points) during the 15-year interval.

    Results:
    The proportion of patients experiencing early disease activity was lower in patients on IM IFNβ-1a than placebo for all disease activity markers (range 23.5%-29.0% vs. 41.0%-45.5%). In the IM IFNβ-1a group, persistent disease activity predicted severe EDSS worsening: gad lesions (OR=8.96, p<0.001); relapses (OR=4.44, p=0.010); and new T2 lesions (OR=2.90, p=0.080). In placebo patients, early disease activity was not as strongly associated with long-term outcomes (OR range=1.53-2.62, p=0.069-0.408).

    Interpretation:
    Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ treated patients with MRI, and for changing therapy in patients with active disease.

    Robert A. Bermel MD, Xiaojun You PhD, Pamela Foulds MD, Robert Hyde, Jack H. Simon MD, Elizabeth Fisher PhD, Richard A. Rudick MD

    Full Article

    Source: Doctors Lounge Copyright © 2001-2012 Doctors Lounge (28/09/12)

    RebiSlide(TM), Rebif(R) multidose manual pen-injector for MS announced

    RebislideMerck Serono, a division of Merck, Darmstadt, Germany, announced the forthcoming introduction of the new injection device RebiSlide™ in Europe and Canada, followed by other countries. RebiSlide™ is a multidose manual injection pen for the self-administration of Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS).

    "RebiSlide™ is the latest addition to Merck Serono's range of injection devices for the self-administration of Rebif® to meet the needs of patients looking for a compact and multidose device," said Belén Garijo, Head of Global Operations at Merck Serono.

    "The introduction of RebiSlide™, alongside other innovative devices such as the electronic multidose device RebiSmart™ and the single-use pre-filled pen RebiDose™, underscores our commitment to continuous advancement in multiple sclerosis treatments, by offering patients different administration options to suit their individual needs."

    RebiSlide™ is a manual multidose injection device for MS therapy and was designed to offer an alternative way of injection for patients with relapsing multiple sclerosis looking for a portable and multidose device. RebiSlide™ uses the multidose cartridges of Rebif® containing a week's supply of Rebif® therapy (three doses of 44 micrograms or three doses of 22 micrograms). The device contains a dose window, which allows users to select the dose of injection prescribed, including dose titration (8.8 micrograms or 22 micrograms).

    RebiSlide™ is approved in the European Union, in Australia and in Canada. It was first launched in Hungary and further launches will follow in Italy, Greece and Canada in the next few weeks. In addition to RebiSlide™, Rebif® can be administered with the delivery devices RebiSmart™, RebiDose™ and Rebiject™ II or by manual injection using pre-filled syringes. These devices are not available in all countries.

    About Rebif®
    Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS) and is similar to the interferon beta protein produced by the human body. The efficacy of Rebif® in chronic progressive MS has not been established. Interferons are thought to help reduce inflammation. The exact mechanism is unknown.

    Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 90 countries worldwide. Rebif® has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area*. Rebif® can either be administrated with the RebiSmart™ electronic auto-injection device, or with the RebiDose™ single-use disposable pen, or the manual multidose injection pen RebiSlide™. Rebif® can also be administered with the autoinjector Rebiject™ II or by manual injection using ready-to-use pre-filled syringes. These injection devices are not available in all countries.

    In January 2012, the European commission approved the extension of the indication of Rebif® in early multiple sclerosis. The extension of the indication of Rebif® has not been submitted in the United States.

    Rebif® should be used with caution in patients with a history of depression, liver disease and seizures. Most commonly reported side effects are flu-like symptoms, injection site disorders, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors.

    * The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

    PR Newswire Copyright © 2012 PR Newswire Association LLC (08/06/12)

    Glatiramer-IFN combination in MS bring mixed results

    Disease Modifying DrugsRadiologic findings from a closely watched trial of glatiramer acetate (Copaxone) and interferon-beta-1a (Avonex) combination therapy in relapsing remitting multiple sclerosis were mixed, a researcher said here.

    Compared with the individual drugs given alone for 3 years, the combination was superior in terms of new lesion activity visible on MRI scans and in the accumulation of total lesion volumes, said Jerry Wolinsky, MD, of the University of Texas Health Science Center in Houston.

    But the combination failed to show an advantage over monotherapy in several other key radiological measures, including brain atrophy, volume of normal-appearing grey and white matter, and the so-called Z4 composite score, Wolinsky told attendees at the American Academy of Neurology meeting.

    Clinical results from the CombiRx trial -- which Wolinsky described as "the longest controlled clinical, MRI, and biomarker dataset of any MS trial" -- are to be reported Friday. Unlike most presentations at the meeting, the published abstract contained no information on results.

    Glatiramer acetate and interferon-beta have been the mainstays of multiple sclerosis treatment for many years. Although most patients eventually relapse or progress while taking one of these agents, they usually switch treatments rather than add the other one.

    Session moderator Robert Fox, MD, of the Cleveland Clinic, told MedPage Today that combination treatment is unusual -- for one thing, because the drugs are expensive and insurance seldom pays for both at once.

    With little experience, clinicians have not really known whether combining the two drugs would even be helpful, Fox said.

    The CombiRx trial, funded by the National Institutes of Health, started in 2005, Wolinsky said. A total of 1,008 patients were enrolled through April 2009, with 3-year data finally locked earlier this month.

    Patients were randomized to the three study arms in a 2:1:1 ratio to the combination or to one drug or the other as monotherapy, with a placebo-controlled, double-dummy, and double-blinded design.

    Mean patient age was about 38, with an average disease duration of 4.3 years and just over a year after diagnosis when they enrolled in the study.

    About 40% of patients showed gadolinium-enhancing lesions at enrollment. The average count at baseline was 1.7, with total lesion volume of 12.2 mL and a T1 hypointense lesion volume of 1.7 mL.

    Relative to baseline, patients in all three arms showed improvement on average in each of the major radiologic evaluations. But there was no clear winner among treatments, as Wolinsky explained. For the combination to be considered effective, it had to be significantly superior to the most effective of the monotherapy treatments, and that was mostly not the case.

    The broadest measure was the Z4 composite, which combined MRI measures of gadolinium-enhancing, T1 hypointense, and T2 hyperintense lesions and normalized cerebrospinal fluid volume. There was no significant difference during the trial between the combination and either of the two monotherapies.

    Combination treatment also failed to be clearly superior in several other measures: total gadolinium-enhancing lesion volume over time, the percent of patients free of gadolinium-enhancing lesions at 36 months, total burden of disease, "combined unique activity lesions," total T1 hypointense lesion volume, or intracranial cerebrospinal fluid volume (reflecting brain atrophy).

    As would be expected from a combination of two drugs known to be active against MS lesion activity, it was never the case that the combination was inferior to a monotherapy.

    On the other hand, there was little to suggest that their effects were additive.

    Fox told MedPage Today that it was too early to call the combination a failure. "We'll have to see the clinical results," he said.

    The trial was funded by the National Institutes of Health. Teva and Biogen Idec provided study medications free of charge.

    Wolinsky reported personal payments from Astellas, Bayer, Celgene, Eli Lilly, Roche, Novartis, sanofi-aventis, Teva Neuroscience as consultant and participant on monitoring and advisory boards, and research support from sanofi-aventis.

    Fox reported payments from Avanir, Biogen Idec, EMD Serono, and Novartis, and research support from Biogen Idec and Genentech.

    Primary source: American Academy of Neurology

    Source reference:
    Wolinsky J, et al "The CombiRx trial: A multi-center, double-blind, randomized study comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in participants with relapsing remitting multiple sclerosis – MRI outcomes" AAN 2012; Abstract S10.002.

    Source: MedPage Today © 2012 Everyday Health, Inc (26/04/12)

    Rebif use following first sign of possible MS reduces likelihood of progression to MS

    Rebif People who received injections of the multiple sclerosis (MS) drug interferon beta-1a soon after their first signs of possible MS were less likely to progress to clinically definite MS than people who switched to interferon beta-1a from placebo, according to new phase three results of the three-year REFLEXION clinical trial that will be presented as part of the Emerging Science program (formerly known as Late-Breaking Science) at the American Academy of Neurology's 64th Annual Meeting in New Orleans, April 21 to April 28, 2012.

    The trial was conducted with the human serum albumin-free formulation of interferon beta-1a, which is now available in all European Union countries, Australia, Canada and Switzerland, as well as a number of countries in Asia, Latin America, Africa and the Middle East. It is not available in the United States.

    "While we've known it's beneficial to start MS drugs as soon as possible, this is the first trial to show a benefit of early injections of interferon beta-1a treatment at three years," said Mark Freedman, MD, with the University of Ottawa in Ontario, Canada, and a Fellow of the American Academy of Neurology.

    The three-year clinical trial involved 517 people who had experienced a first clinical episode suggestive of a demyelinating event, such as tingling, numbness, muscle weakness or problems with balance, along with having at least two clinically silent brain lesions detected by a brain MRI scan.

    For two years, one-third of the participants received 44 mcg of interferon beta-1a subcutaneously three times a week; one-third received 44 mcg of the drug once a week, which is an unapproved dosage; and another one-third received placebo for two years or until experiencing a second clinical episode, at which point they were switched to three-times-weekly dosing. After the two years were over, the 133 people who were still receiving the placebo were switched to the three-times-weekly dose and the others continued their originally allocated dosages. The participants started their treatment an average of 58 days after their first symptoms.

    After the third year of the study, the researchers found that those who had been receiving the drug three times a week or once a week for the duration of the trial were less likely to be diagnosed with clinically definite MS (defined as having a second clinical attack or a sustained increase in the Expanded Disability Status Scale disability score of greater than 1.5) than those who had initially received the placebo. The cumulative probability of being diagnosed with clinically definite MS by the end of the third year was 41 percent for the delayed treatment group (people who had switched from placebo to three-times-weekly treatment), 28 percent for those who had received once-a-week treatment all three years, and 27 percent for those who had three-times-weekly treatment for three years.

    The study also found that those who had received the treatment for the full three years were less likely to meet the McDonald criteria for a MS diagnosis, a different measure than the one for clinically definite MS that includes an evaluation of MRI. A total of 87 percent of people who had switched from placebo to the treatment after two years met the McDonald criteria for MS after three years, compared with 79 percent of those who had received the weekly treatment and 67 percent of those who had treatments three times a week.

    "While doses three times a week and once a week equally delayed a clinically definite MS diagnosis without MRI measures, there were significantly more benefits in taking the drug three times a week compared with once a week when it came to brain lesion changes and other McDonald criteria for diagnosing MS," said Freedman.

    The REFLEXION trial is ongoing and will provide long-term data out to five years.

    The most common adverse events in the trial were flu-like symptoms, injection site reactions and headache.

    The study was supported by Merck Serono S.A. – Geneva, Switzerland.

    Source: Drugs.com Copyright © 2000-2012 Drugs.com. All rights reserved (20/04/12)

    EC approval for Rebif use extension for early Multiple Sclerosis

    RebifMerck KGaA said the European Commission or EC has approved extension of the indication of Rebif, a treatment for relapsing forms of multiple sclerosis or MS. This EC approval, based on REFLEX study results, is for the use of Rebif 44 micrograms three times weekly in patients who have experienced a single demyelinating event, an early sign of the disease, and who are at high risk of converting to MS.

    Annalisa Jenkins, Head of Global Drug Development and Medical at the Merck Serono division. "Multiple sclerosis has an initial stage when clinical manifestations are not pronounced but irreversible neurological damage is taking place. Throughout the European Union, neurologists will now be able to prescribe Rebif for patients with early signs of this devastating disease."

    The new labelling for Rebif is valid immediately in all 27 member states of the European Union. The company still invests in discovering and developing treatment options in this area, including active life-cycle management initiatives for Merck's foundation therapy, Rebif, as well as strengthening its existing and establish new collaborations to advance research and bring innovative solutions to patients living with MS.

    Source: RTT News Copyright © 2012 RTTNews (25/01/12)

    CHMP gives positive opinion for extended indication for Rebif® for patients with early signs of MS

    RebifMerck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that it received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), for its variation application to extend the indication of Rebif (interferon beta-1a), its leading treatment for relapsing forms of multiple sclerosis (MS).

    The positive CHMP opinion is for the use of Rebif 44 micrograms three times weekly in patients who have experienced a single demyelinating event, an early sign of the disease, and who are at high risk of converting to MS.

    "This is an important step towards making Rebif available across Europe to patients with early signs of multiple sclerosis," said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical at Merck Serono. "It is part of our on-going commitment to improving access to Rebif for patients with this devastating disease, and supporting its appropriate use."

    In addition to updating the indication section, the CHMP recommendation includes an update of the posology section adding the approved posology of Rebif in the first demyelinating event indication, and an update of the pharmacodynamic properties section summarising the design of the REFLEX[1] study together with its main results. The CHMP recommendation provides the basis for an amendment of the marketing authorisation to reflect the variation by the European Commission, which is expected within three months from the opinion.

    The submission of a type II variation to extend the indication of Rebif was supported by the results of the REFLEX study. The REFLEX study was conducted with the HSA-free[2] formulation of Rebif, which is now available in all European Union countries, Australia, Canada and Switzerland, as well as a number of countries in Asia, Latin America, Africa and the Middle East. The HSA-free formulation of Rebif is not available in the United States.

    Merck Serono has a long-standing commitment to the therapeutic area of MS. The company continues to invest in discovering and developing treatment options in this area, including active life-cycle management initiatives targeting numerous aspects of Merck Serono's foundation therapy Rebif (formulation, indication, delivery devices). In addition, the company continues to strengthen existing - and identify new - collaborations to advance research and bring therapies to market.

    [1]REFLEX: REbif FLEXible dosing in early multiple sclerosis: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial of the HSA-free formulation of Rebif (44 micrograms three times a week and 44 micrograms once a week) in Subjects at High Risk of Converting to Multiple Sclerosis

    [2]HSA-free formulation of Rebif = human serum albumin-free formulation of Rebif

    Source: Science 2.0 © 2011 ION Publications LLC (21/11/11)

    MS markers match disability progression in Rebif study

    RebifTwo surrogate markers commonly used in multiple sclerosis (MS) clinical trials are near-perfect measures of the effect of treatment with interferon, researchers reported.
    In a statistical analysis of patients in a major clinical trial, the two markers -- T2 lesions seen on MRI and relapses -- accounted for all of the effect of interferon ß-1a on disease progression, according to Maria Pia Sormani, PhD, of the University of Genoa in Italy, and colleagues.

    The findings provide "strong scientific support" for the use of the two markers in clinical trials of interferon and drugs with a similar mechanism, Sormani and colleagues reported in the November 1 issue of Neurology.

    Among other things, they suggest that increasing the size or duration of trials in order to gain power to assess disability endpoints is not needed, because the full effect on disability over two years of follow up is accounted for by a year of observation of MRI lesions and relapses during treatment.

    The information may have important implications in the next few years as interferon-beta comes off patent and regulatory agencies contemplate licensing similar drugs, they added.

    While the two markers have been widely used, they have been controversial, so the researchers analyzed patient data from the large PRISMS study -- short for Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis.

    That study, reported in 1998, enrolled 560 patients with relapsing-remitting, MS and assigned them randomly to get either interferon or a placebo subcutaneously three times a week for two years.

    The primary endpoint was disability, as defined by the Expanded Disability Status Scale over two years of follow up, but the original researchers also tracked changes in lesions on MRI and the number of relapses.

    Using patient-level data from the trial, Sormani and colleagues reported that:

    Treatment with interferon, compared with placebo, reduced the odds of a worsening disability score by 31% over two years, which was significant at P=0.049

    Treatment also reduced the mean number of MRI lesions by 61% and the mean number of relapses by 36% over a year. Both differences from placebo were significant at P<0.0001

    The proportion of treatment effect accounted for by lesions was 63%, while the proportion accounted for by relapses was 61%, when the markers were considered independently

    Taken together, the two markers accounted for 100% of the treatment effect, although the low end of the confidence interval was only 32%
    The researchers cautioned that the finding only applied to studies involving interferon-beta or drugs with a similar mechanism and, "cannot be extended to all MS therapies, even though they may prove useful in interpreting the outcomes of future MS trials."

    Indeed, "among the challenges ahead" will be to conduct similar analyses for other MS-modifying drugs, according to Jerry Wolinsky, MD, of the University of Texas Health Science Center in Houston, and Christopher Beck, PhD, of the University of Rochester Medical Center in Rochester, N.Y.

    In an accompanying editorial, they argued that the study does not rule out the possibility that the two markers are actually a poor surrogate for disability, because the lower end of the confidence interval allows for a proportion of treatment effect of just 32%.

    The study had support from Merck Serono S.A. Sormani reported financial links with Biogen Idec, Merck Serono, Actelion Pharmaceuticals, Synthon, and Teva Pharmaceutical Industries. Several authors are employees of Merck.

    Wolinsky reported financial links with Astellas Pharma, Bayer Schering Pharma, Celgene, Eli Lilly and Company, Roche, Teva Pharmaceutical Industries, Actelion Pharmaceuticals, Facet Biotech, Genentech, Genzyme, Novartis, Peptimmune, UCB, Biogen Idec, sanofi-aventis, and Millipore (Chemicon International) Corp.

    Beck reported financial links with Amarin, Guidant, and Boston Scientific.

    Primary source: Neurology
    Source reference:
    Sormani MP, et al "Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis" Neurology 2011; 77: 1684–1690.

    Additional source: Neurology
    Source reference:
    Wolinsky JS, Beck CA "The long march to surrogates of meaningful clinical outcomes in MS trials: Are we there yet?" Neurology 2011; 77: 1658–1659.

    Source: Medpage Today © 2011 Everyday Health, Inc. (04/11/11)

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