What is Campath-1H?

Campath-1H is a drug called alemtuzumab. It is an anti-CD52 monoclonal antibody and is marketed under the names Campath and Mabcampath.

Campath-1H is a potentially new treatment for Multiple Sclerosis or MS. It is currently undergoing trials in the UK, USA, Italy and Croatia to determine whether it can help those with an early form of MS. The drug is a monoclonal antibody designed to target that part of the immune system which is assumed to be harming people with MS. Campath's scientific name is alemtuzumab and it is currently manufactured by ILEX Pharmaceuticals and distributed by Berlex Laboratories. It has been developed for a number of years, and has already been used as a treatment for B-cell chronic lymphocytic leukaemia.

You can read about people's experiences on Campath within the What Has Helped You section of the website.

Genzyme Corporation announced that its alemtuzumab for multiple sclerosis development program has been granted Fast Track status by the U.S. Food and Drug Administration (FDA).

This designation covers patients with relapsing-remitting forms of the disease.

The FDA's Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Under Fast Track designation, alemtuzumab for MS is eligible for Priority Review and the FDA may consider for review portions of the marketing application before the submission of a New Drug Application (NDA) is completed.

"We are extremely pleased that our alemtuzumab development program has been assigned Fast Track status, and look forward to working closely with the FDA to expedite the program's review process," said Henri Termeer, Genzyme's chairman and chief executive officer. "Alemtuzumab is a potentially transformative therapy for the treatment of multiple sclerosis, and an important part of our future."

Alemtuzumab for the treatment of MS is currently being evaluated in two pivotal multi-center, multi-national trials, known as CARE-MS SM (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis). The company's CARE-MS I Phase 3 trial is a randomized study comparing alemtuzumab to the approved therapy Rebif (high-dose interferon beta-1a) in early, relapsing-remitting multiple sclerosis (RRMS) patients who have received no prior therapy. The second Phase 3 trial, CARE-MS II, is comparing alemtuzumab to Rebif in RRMS patients who had active disease while on other MS therapies.

Both trials are fully enrolled and data are expected to be available in 2011.

About Campath® (alemtuzumab)
Campath® is licensed in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the treatment of B-CLL in patients who have been treated with alkylating agents and for whom fludarabine combination therapy is not appropriate. The product was launched in its oncology indication in 2001 in the US, where it is marketed as Campath®, and in Europe, where it is named MabCampath®.

Campath for B-CLL has a boxed warning that includes information on cytopenias, infusion reactions, and infections. The most commonly reported adverse reactions in patients with B-CLL were infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

Source: World Pharma News © World Pharma News (15/06/10)

Genzyme Corporation reported four-year follow-up data from its completed Phase 2 multiple sclerosis (MS) trial showing an estimated 71 percent of alemtuzumab treated patients remain free of clinically-active disease as much as three years after most patients received their last course of the investigational compound. The data were presented at the American Academy of Neurology annual meeting.

The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif(R) (interferon beta-1a) in early, active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy. In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years.

Results of the four-year review found:

-- an estimated 71 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking Rebif (p<0.001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without progression of disability as measured by the Expanded Disability Status Scale (EDSS) throughout the course of the study;

-- an estimated 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 68 percent of patients taking Rebif; and

-- an estimated 77 percent of alemtuzumab-treated patients were relapse-free compared to 49 percent of patients taking Rebif.

"These early data may set a new bar for clinical outcomes in multiple sclerosis," said Omar Khan, MD, Professor of Neurology, Wayne State University School of Medicine, site principal investigator in the CAMMS223 Phase 2 trial.

Post-hoc analyses of the patients free from clinically-active disease were performed using data obtained from patients participating in CAMMS223. The dataset analyzed consists of the originally-planned three years of patient follow-up, additional continuous post-three-year follow-up, and prospective follow-up of patients who initially discontinued but returned to the study to participate in the risk management program. Roughly 15 percent of patients participating in the post-three-year follow-up used non-study MS disease modifying therapies. A sensitivity analysis that censored these patients found that the risk of relapse, sustained accumulation of disability, and free from clinically-active disease status favored alemtuzumab.

Alemtuzumab Mechanism of Action Data

Research suggests that in multiple sclerosis, T- and B-lymphocytes mistakenly attack the myelin sheath that protects nerve cells. These attacks can lead to disease progression and irreversible disability. The first detailed depiction of pharmacodynamic data from a large cohort of alemtuzumab treated relapsing-remitting MS patients (n=216) provided at AAN showed that alemtuzumab, in a selective fashion, targets T- and B-lymphocytes while largely sparing other immune system elements. The analysis also found that the targeted immune system cells begin to repopulate following treatment.

"We believe that alemtuzumab targets the immune system cells responsible for the cellular damage found in multiple sclerosis, while sparing other immune system elements," said Alasdair Coles, MD, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge, a lead investigator of the Phase 2 clinical trial and author of the leukocyte dynamics abstract.

Updated Safety Findings

Immune thrombocytopenic purpura (ITP), an autoimmune disease, was identified in six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial. Symptoms of ITP went unrecognized in the first alemtuzumab case and led to the onset of a fatal cerebral hemorrhage. Five other alemtuzumab-related cases were subsequently diagnosed and all five patients achieved durable remission, both with and without treatment during the Phase 2 study. New follow-up data presented at AAN show that these five patients continue to have normal platelet counts, and ITP has not been identified more than 16 months following the last alemtuzumab cycle. There have been no additional or recurrent events of ITP reported in the Phase 2 trial to-date.

"In this study, alemtuzumab treated patients who experienced an ITP event and achieved remission have had no recurring episodes of ITP. The remissions were complete and durable," said abstract author Edward Fox, MD, PhD, Director of the Multiple Sclerosis Clinic of Central Texas, and a clinical site director for the Phase 2 and 3 trials.

Additional new follow-up data presented at AAN show that the alemtuzumab-treated patients who experienced an autoimmune adverse event still experienced clinical benefits. Alemtuzumab patients with autoimmune adverse events had a 78 percent reduced rate of relapse, and 66 percent reduced risk for sustained accumulation of disability, compared to Rebif patients. Updated four-year data from the Phase 2 trial found that approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. These events either normalized spontaneously or were managed using conventional therapies.

Genzyme is conducting two Phase 3 pivotal trials to evaluate alemtuzumab in the treatment of MS. Both trials completed enrollment in 2009. CARE-MS I, a randomized trial comparing alemtuzumab to Rebif, is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other MS therapies. Patients who enrolled in those trials beginning in 2007 have completed the protocol-specified two years of follow-up and have begun to transfer into an extension trial. Data from the Phase 3 trials are expected to be available in 2011.

About CAMMS223 Phase 2 Study

In the Phase 2 trial, 334 patients with active RRMS were randomized to treatment with alemtuzumab at one of two dose levels, or Rebif. Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Of the original sample, 158 patients completed a month 48 study visit (alemtuzumab n=122; interferon beta-1a: n=36). Alemtuzumab and Rebif were not provided by the study after the third year. Patients were allowed to continue Rebif or to receive other disease-modifying therapies during this follow-up period. The majority of patients last received alemtuzumab at Month 12.

Common adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, particularly of the upper respiratory tract; infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections. Patient monitoring for thyroid disorders, ITP, and anti-GBM disease is incorporated into all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

Alemtuzumab is an investigational drug for the treatment of MS and must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

Source: Genzyme Corporation (14/04/10)

Genzyme Corp. said that four-year follow-up data from its completed Phase 2 multiple sclerosis trial continued to show durable reductions in relapse rate and sustained accumulation of disability three years after the majority of patients received their last course of the investigational compound alemtuzumab.

The accumulated four-year efficacy and safety data from the Phase 2 trial was presented at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting in Germany.

The Phase 2 trial compared alemtuzumab to an approved multiple sclerosis therapy Rebif in early, relapsing-remitting multiple sclerosis or RRMS patients who had received no prior therapy. Three-year trial data were reported in the New England Journal of Medicine in last October.

In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three-times per week, every week for three years.

The four-year analysis of early RRMS patients from the trial found that patients taking once-yearly cycles of alemtuzumab reduced their risk of relapse by 72% and the risk of sustained accumulation of disability by 73% compared to patients treated with the active comparator Rebif. These data closely mirror the three-year findings reported in the NEJM manuscript. Further, the annualized relapse rate and disability risk measured from year three to four remained at the same low level observed in prior years of the study.
 
Genzyme also announced that its CARE-MS II Phase 3 trial, one of two pivotal trials of alemtuzumab in the treatment of multiple sclerosis, has completed enrollment. CARE-MS I Phase 3 trial, a randomized trial comparing alemtuzumab to Rebif, completed enrollment earlier this year. CARE-MS I is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other multiple sclerosis therapies.

Patients who enrolled at the start of both trials in 2007 will soon complete the protocol-specified two years of follow-up and begin to move into an extension trial which allows patients previously treated with Rebif to receive alemtuzumab. Patients previously treated with alemtuzumab will be allowed to take another treatment cycle as needed, said Genzyme.

Source: RTT News © 2009 RTTNews. (12/09/09)

Genzyme Corp. announced that it has completed the transaction with Bayer HealthCare to acquire the worldwide rights to Campath®/MabCampath® (alemtuzumab), giving Genzyme primary responsibility for the development and commercialisation of this promising multiple sclerosis (MS) therapeutic candidate. Genzyme is conducting two rapidly progressing phase 3 studies of alemtuzumab in relapsing-remitting MS patients.

"Alemtuzumab for multiple sclerosis is a potential significant therapeutic advance for patients, and we are pleased to be leading this program that we expect will provide an important catalyst for the company’s long-term growth.”

Under the terms of the transaction, Genzyme will make no upfront payment to Bayer. In exchange for the rights to alemtuzumab, Genzyme will make payments to Bayer following product approval under an earn-out arrangement that is based on product revenue. Similarly, in exchange for the rights to Campath, Genzyme will make future payments based upon revenue. 

MS Development

Genzyme is now leading the development program for alemtuzumab in MS, and following approval, will have primary responsibility for its commercialization.

Alemtuzumab in MS is in two phase 3 trials. The first trial, for which enrollment is complete, treats early, active relapsing-remitting patients who have received no prior therapy. The second study, which is expected to complete enrollment before the end of this year, is studying relapsing-remitting patients who had active disease while on other MS therapies. Data from the trials are expected to be available in 2011, and approval is anticipated in 2012.

Bayer, which has been co-developing alemtuzumab in MS with Genzyme, will continue to fund development at current levels until the investigational compound is approved for this indication.

Source: Genzyme Corp. (02/06/09)

Genzyme Corp. has announced an agreement with Bayer HealthCare to acquire the worldwide rights of Campath, or alemtuzumab. The deal will give Genzyme primary responsibility for the development and commercialisation of Campath for the treatment of multiple sclerosis, or MS.

Bayer will continue to fund a portion of the drug's development in MS and will retain an option to co-promote the product in MS upon approval. The deal is structured as an earn-out arrangement. Bayer will receive payments based on revenues and potential milestone payments if cumulative revenue targets are achieved. There are no upfront payments for the rights of these three drugs.

In addition, Genzyme will assume sole responsibility for the worldwide sales and marketing of Campath in B-cell chronic lymphocytic leukemia, or CLL. Meanwhile, Bayer will retain the right to develop and commercialise alemtuzumab in solid organ transplant indications.

Genzyme said the transaction is accretive and has already reflected in the company's 2009 revenue and non-GAAP earnings per share guidance. The deal also supports the company's goal of 20% compound average non-GAAP earnings growth from 2006 to 2011.

Source: RTT News © 2009 RTTNews(01/04/09)

When news broke in October that an approved cancer therapy had, for the first time, halted the progress of multiple sclerosis (MS), excitement was tangible among clinicians and patient groups. The phase 2 study's results are certainly unprecedented in MS. But whether Campath (alemtuzumab), a monoclonal antibody (mAb) already approved to treat leukemia, actually 'reverses' MS, as some news stories in the mainstream media trumpeted, and how it works remain unresolved. The next two years are expected to reveal much about not only Campath in MS, but also the competitive landscape for this indication where the tradeoff between efficacy and safety remains a tough hurdle for drug developers.

Campath was the first humanized mAb to be developed as a therapy. It has a long, illustrious history, dating back over two decades to anti-lymphocyte rat antibodies first raised by Herman Waldman and Geoffrey Hale (Mol. Biol. Med. 3, 305–319, 1983). The name Campath derives from the pathology department at Cambridge University, UK, where the academics worked.

The monoclonal was raised to target B and T cells and was initially pursued as treatment for graft-versus-host disease. However, Campath took off as a therapeutic only when Greg Winter and colleagues, also at Cambridge University, humanized the recombinant DNA-derived antibody, which became known as alemtuzumab.

Campath targets the cell surface glycoprotein CD52 present on all mature lymphocytes and has been used to treat B-cell chronic lymphocytic leukemia since 2001 when it was approved. The notion that Campath might also work as a treatment for MS was pioneered in 1991 by Alistair Compston, at Cambridge University, UK, also the lead investigator in the recent New England Journal of Medicine study (N. Engl. J. Med. 359, 1786, 2008). He speculated that the antibody might work by destroying the mature T and B lymphocytes that drive the autoimmune attack against nerves and brain tissue in MS patients. After treatment, the immune system would be replenished, but this time, without the auto-reactive lymphocytes.

The strategy is indeed promising. Results from the latest study, funded by Cambridge, Massachusetts–based Genzyme and partner Bayer Schering, of Leverkusen, Germany, look "extremely attractive," says Jerry Wolinsky, who directs the Multiple Sclerosis Research Group at the University of Texas Health Science Center in Houston.

In the phase 2 trial, known as CAMMS223, Campath was administered once yearly to 334 previously untreated individuals with early relapsing-remitting MS. This regime cut patients' risk of relapse by 74% and reduced the rate of sustained accumulation of disability by 71%, compared with patients treated with the standard treatment Rebif, a high-dose interferon -1a from Merck Serono. Patients were followed for three years; those on Campath scored higher on a standard disability scale than before starting the treatment, whereas patients on Rebif deteriorated. The benefits were long lived, lasting at least three years.

Even more striking, perhaps, are the magnetic resonance imaging scans that suggest the drug may be reversing the symptoms of the disease. Imaging data revealed that people in the Campath arm increased brain volume after a year, whereas the brain volume in the group receiving standard interferon experienced a decline.

"We're not saying people are cured," cautions neurologist David Margolin, Genzyme's lead medical monitor in the phase 2 and ongoing phase 3 program. But Campath patients' disability scores improved dramatically "within a few months, and this is not driven by just a few individuals," adds Margolin, who has an MS specialty practice at Massachusetts General Hospital and the Brigham and Women's Hospital in Boston. "Clearly, there is some recovery occurring, only in the [Campath] population as a group. Thirty percent of Rebif patients improved, but more of them worsened," whereas Campath achieved "remarkable stabilization" of disease. The other benefit of Campath is its once-yearly administration.

"It's not reversing MS," says Lauren Krupp, neurologist at Stony Brook University Hospital in New York and director of the Pediatric Multiple Sclerosis Comprehensive Care Center, who is nonetheless guardedly optimistic. "You have patients with relapses and remissions. If you get rid of the relapses, then over time, it's going to look like there is less [of a] persistent neurologic deficit. It's just a function of the drug's effects on the relapses, rather than turning the disease around."

The claims of disease reversal regarding Campath are still "a big stretch," says Wolinksy, who points out that the extrapolations are made by hopeful onlookers and boosters and not by the drug makers Genzyme and Bayer Schering. "The absolute good news is, if we treat early and aggressively, we can expect remarkable outcomes, but at a cost for a fair percentage of patients."

Clinicians and regulators worry over side effects, particularly the risk of developing a rare neurological condition progressive multifocal leukoencephalopathy (PML), the brain infection that bedevils the -4 integrin antagonist Tysabri (natalizumab), co-marketed by Biogen Idec, of Cambridge, Massachusetts, and Dublin-based Elan. Thus far, no cases of PML have shown up in MS patients exposed to Campath. Years of experience using Campath for chronic lymphocytic leukemia treatment may not be informative as patients with this form of leukemia can develop PML, independently of Campath.

Despite the troubles associated with Tysabri, people with MS may still retain "an overall positive view" toward the treatment, says David Williams, head of business development for PatientsLikeMe, an online health community for patients with life-changing conditions including MS. "Campath will be the same way, if it's approved," Williams predicts, though the risks as known so far are hardly identical.

With Campath, safety issues could arise over a potentially fatal autoimmune disorder. In the phase 2 trials, 20% of Campath-treated patients developed thyroid disorders compared to 3% on Rebif. Krupp notes, however, that thyroid trouble seems to occur with MS anyway, for reasons that are not well understood. More serious is the development of immune thrombocytopenic purpura (ITP). Three patients in the Campath group developed this complication and one of them died. "Some people would suggest management of ITP is easy, but if it were straightforward and easy, they wouldn't have had the first one die," Wolinsky says. Margolin notes that the fatal case of ITP—the first to arise —"took everyone by surprise," whereas the others fully recovered with treatment, and one did so spontaneously. Krupp, for her patients, "would consider [Campath] in patients where all of those things, as bad as they sound, are 'not as bad' as what's happening with their MS."

Other promising mAbs in late-stage development for MS include Rituxan (rituximab), an approved therapy for rheumatoid arthritis and non-Hodgkin's lymphoma from Biogen and S. San Francisco, California–based Genentech, in phase 3 trials. Another drug currently in phase 2 studies is Zenapax (daclizumab), an immunosuppressant mAb for organ transplants from Biogen and PDL Biopharma of Fremont, California. Leerink Swann analyst William Tanner wrote in a September research report that consultants were "not overly impressed" with Zenapax, holding out hopes for other compounds, though the safety profile of Campath may be of concern. Still in the game, but just barely, is Basel–based Novartis' S1P1 modulator FTY720 (fingolimod), which has run into serious safety issues in pivotal testing.

For Campath, efficacy could win over safety concerns. One phase 3 trial aims to enroll 525 patients like those in phase 2 with early, relapsing, remitting disease; the other will test relapsing MS patients and intends to enroll 1,200. Campath could be filed for approval with the FDA as early as 2011, probably as a monotherapy. "With the findings to date, I don't see any reason to add another drug," Margolin says, though some neurologists speculate that Campath might be used as induction therapy, to be followed by interferon or Copaxone (glatiramer).

An ongoing debate in MS therapy is how the disease's inflammatory and neurodegenerative aspects overlap and what this means for drug developers. "None of these drugs are going to fix neurons that are dead and gone, but some probably will help to slow the neurodegenerative processes," Margolin says. "We hope our trials will establish Campath as the treatment of choice, if patients are relapsing."

Source: nature biotechnology © 2009 Nature Publishing Group (16/01/09)

Multiple Sclerosis patients have significant and sustained reduction in disability and risk of relapse on Alemtuzumab versus Rebif(R).

Genzyme Corporation and Bayer HealthCare Pharmaceuticals Inc. today announced study results showing that patients with early relapsing-remitting multiple sclerosis (RRMS) taking once-yearly cycles of alemtuzumab reduced their risk of relapse by 74 percent and the risk of sustained accumulation of disability by 71 percent compared to patients treated with the active comparator Rebif® (high-dose interferon beta-1a).

Importantly, the mean disability of patients on alemtuzumab improved from baseline, whereas the mean disability of those on Rebif worsened. The treatment benefits of alemtuzumab were sustained for at least three years, even though the majority of alemtuzumab-treated patients were last dosed two years earlier. These results come from the final three-year analysis of a Phase 2 clinical study (CAMMS223) reported in the Oct. 23 issue of the New England Journal of Medicine. The study involved 334 patients who had not previously been treated for their disease.

“The alemtuzumab trial data continue to suggest a potentially new and exciting treatment for patients with early, active multiple sclerosis,” says Alastair Compston, Professor of Neurology and the head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom, and the study’s principal investigator. “This randomized study confirms findings from prior studies demonstrating that treatment with alemtuzumab can have a profound and durable impact on patients with relapsing-remitting multiple sclerosis, including restoring some lost function in many patients.”

“Symptoms of multiple sclerosis result from an immune system attack on the protective insulation surrounding nerve fibers of the central nervous system. We believe alemtuzumab shuts down this immune system attack, treating the disease at its root cause,” says Alasdair Coles, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge and a lead investigator in the study.

Common non-serious adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, which were predominantly mild to moderate in severity, as well as autoimmune thyroid disease. Three percent of alemtuzumab-treated patients developed the potentially serious autoimmune adverse event immune thrombocytopenic purpura (ITP), a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. Additional study and trial safety information is below.

“The trial was larger and follow-up was longer than the typical Phase 2 trial in multiple sclerosis. It is important to note that we compared the investigative drug directly against a widely used therapy rather than against placebo. The trial did not show an increased risk of life-threatening or opportunistic infections, but a proportion of alemtuzumab patients experienced new autoimmune disease. We have been able to create a robust patient monitoring program that allows us to proceed into our two international Phase 3 trials with greater assurance on safety associated with patient management,” says Dr. Richard Moscicki, chief medical officer for Genzyme.

According to the National Multiple Sclerosis Society, approximately 400,000 Americans acknowledge having MS, and every week about 200 people are diagnosed. Worldwide, multiple sclerosis may affect 2.5 million individuals. The disease causes a wide range of symptoms including difficulty with walking, numbness, fatigue and impairment of vision, and progresses to permanent, severe disability in the majority of patients. Relapsing-remitting MS is the most common presenting form of the disease.

“We are pleased to see potential new treatment options move positively through the MS pipeline,” says Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society, “and as alemtuzumab is moved into Phase 3 studies, we hope that individuals with MS will consult with their physicians to assess whether they are appropriate patients and if so will consider the pros and cons of participating in these important clinical trials.”

Helen Yates of the MSRC said: "The work that Professor Alastair Compston and his team have been doing with Alemtuzumab has looked interesting for some time.  This latest news is very exciting indeed and has huge significance in the treatment of relapsing remitting MS. 

Although there are some significant potential side effects the clinicians seem to have learned to control or treat these and the potential benefits do seem to outweigh the risks."

Additional New Top-Line Data

New and previously unreported top-line data from secondary analyses of the CAMMS223 Phase 2 clinical trial, presented last month at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRIMS), revealed that the proportion of clinically disease-free patients was significantly higher in the alemtuzumab group than in the Rebif group at year one (86 percent vs. 63 percent), year two (81 percent vs. 48 percent), and year three (71 percent vs. 39 percent, p-values <0.0001). “Clinically disease-free” was defined as the absence of both relapses and sustained accumulation of disability during the time-period assessed.

The top-line data from WCTRIMS also showed that the proportion of patients free of sustained accumulation of disability over a six-month period was also significantly greater in the alemtuzumab group than in the Rebif group at year one (97.2 percent vs. 87.0 percent), year two (94.3 percent vs. 82.4 percent), and year three (91.0 percent vs. 73.8 percent, p-values <0.005).

Further, the proportion of relapse-free patients over time was significantly greater in the alemtuzumab group than in the Rebif group at year one (91.1 percent vs. 69.3 percent), year two (88.2 percent vs. 58.5), and year three (80.2 percent vs. 51.6 percent, p-values <0.0001).

Phase 2 Extension Trial

Genzyme with Bayer support has launched an extension of the CAMMS223 trial to examine safety and efficacy outcomes beyond three years, and to compare two distinct retreatment strategies. The results should provide an understanding of the long-term effects of prior alemtuzumab treatment as well as the safety and sustained efficacy of additional alemtuzumab retreatment delivered in fixed annual cycles or as needed for resumed MS disease activity. In the fixed arm, patients will receive two annual cycles of alemtuzumab (12 mg/day for three consecutive days/cycle). In the as-needed arm, retreatment is deferred until a patient relapses or develops two or more new/active brain lesions on MRI.

Phase 3 Trials

Genzyme with Bayer support is sponsoring two Phase 3 trials in which patients are now enrolling. The CARE-MS I Phase 3 study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), is a randomized, rater-blinded study that will again compare alemtuzumab to Rebif in patients with relapsing-remitting MS who have not been previously treated for their disease. The CARE-MS II trial is studying patients who have continued to relapse while using approved MS therapies.

About Study CAMMS223

In the Phase 2 trial, 334 patients with active relapsing-remitting multiple sclerosis were enrolled at 49 medical centers in Europe and the United States. Patients in the trial were randomized to treatment with alemtuzumab at one of two dose levels (12 or 24 mg per day intravenously) for five days during the first cycle and three days 12 months later during the second cycle of therapy, or Rebif (44 mcg administered by subcutaneous injection three times per week, as indicated in its product label). A third cycle of alemtuzumab therapy was received by 46 patients at month 24.

The trial compared the efficacy of alemtuzumab with Rebif using two primary outcome measures: the Relapse Rate and the time to Sustained Accumulation of Disability as evidenced by an increase in the Expanded Disability Status Scale (EDSS) score for six consecutive months. Efficacy assessments were made by independent neurologists blinded to patients’ treatment assignments. The EDSS is a 10-point scale in which every 0.5-point step marks a notable deterioration in neurological capabilities.

The mean disability score of patients after alemtuzumab actually improved (by 0.39 EDSS points) indicating a recovery of neurologic functions. The median disability score improved to a similar extent after alemtuzumab. In contrast, mean disability worsened in the Rebif group (by 0.38 EDSS points) resulting in a difference of nearly a full EDSS point (0.77 difference, p<0.0001) at three years.

Safety Data

A total of six alemtuzumab-treated patients, and one Rebif-treated patient, in this study developed a serious adverse event, immune thrombocytopenic purpura (ITP). ITP is a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. The Rebif patient with ITP was asymptomatic but ITP persisted at the time of study completion. In the previously reported alemtuzumab-related fatal case, symptoms of ITP were experienced but were not recognized in time, thus delaying medical attention. Of the remaining alemtuzumab cases, four patients were diagnosed promptly, responded well to medical treatment, and have been stable without a need for ongoing treatment. The other alemtuzumab-treated case experienced spontaneous remission of ITP. A patient monitoring program was instituted in the trial, and there have been no new cases of ITP reported in CAMMS223 in approximately two years.

Common non-serious adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, particularly of the upper respiratory tract; infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections. Though alemtuzumab transiently lowers white blood cell counts, the trial did not show an increased risk of opportunistic infections. Serious infections were infrequent in the alemtuzumab-treated patients. Approximately 23 percent of alemtuzumab-treated patients developed autoimmune thyroid-related adverse events, including Graves’ disease, and were managed using conventional therapies.

Alemtuzumab is an investigational drug for the treatment of MS and must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

Source: Genzyme Corporation & Multiple Sclerosis Resource Centre (23/10/08)

Charcot Award Lecture

Top-line, three-year data from a completed international, multi-center, Phase 2 clinical trial known as CAMMS223 that compared alemtuzumab with Rebif(R) (interferon beta-1a) for the treatment of multiple sclerosis will be presented on Sunday, Oct. 14 at 10 a.m. The data will be presented by Professor Alastair Compston during the prestigious Charcot Award lecture. The study results, taken at 36 months, compare alemtuzumab-treated patients with Rebif(R)-treated patients in the risk for sustained accumulation of disability and the risk for relapse. The data come from a pre-specified analysis conducted after three years of treatment for 334 patients in the study.

Details on two poster presentations -- Alemtuzumab Improved Multiple Sclerosis Functional Composite Scores and Delayed Time to First Relapse at 2-Year Interim Analysis Compared to Subcutaneous Interferon Beta 1-a. Sat. October 13 from 3:30-5:00 p.m. Alasdair J. Coles, M.D.

A further analysis of disability in CAMMS223, as measured by the Multiple Sclerosis Functional Composite Scale (MSFC), will be reported at ECTRIMS. Data from this scale, including quantitative tests on ambulation, manual dexterity, and cognition, will be presented along with new analyses of relapse events. These results build on the two-year analyses of the co-primary endpoints presented at the American Academy of Neurology annual meeting in May, 2007, which demonstrated that the risk of sustained accumulation of disability as well as the annualized relapse rate were markedly reduced in alemtuzumab-treated patients compared to Rebif-treated patients. Data from CAMMS223 provide the rationale for the newly initiated Phase 3 CARE-MS I clinical trial in untreated patients with relapsing-remitting multiple sclerosis.

-- Two-year Results with Alemtuzumab in Patients with Active Relapsing- Remitting Multiple Sclerosis Who Have Failed Licensed Beta-Interferon Therapies. Saturday, October 13 from 3:30-5:00 p.m. Ed Fox, M.D.

In another poster presentation, data from an investigator-sponsored study demonstrate the benefits of alemtuzumab in previously treated MS patients. Data from this two-year study evaluate the effect of two annual cycles of alemtuzumab on patients with relapsing-remitting MS who had failed prior treatment with licensed beta-interferons. Reported at ECTRIMS will be new data on patient functioning as measured by the Multiple Sclerosis Functional Composite Scale cited above. Data from this study provides the basis for the second Phase 3 clinical trial, CARE-MS II, in patients who have continued to relapse while using a licensed therapy. This study is also open to enrollment.

Source: Genzyme Corporation and Bayer Schering Pharma AG, Germany (12/10/07)

The CARE-MS I trial (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), a randomised, rater-blinded study, will compare alemtuzumab to Rebif(R) (interferon beta-1a) in patients with relapsing- remitting multiple sclerosis (MS). Alemtuzumab will be given in two annual cycles; Rebif will be administered three times per week. The CARE-MS I study will include patients who have been diagnosed with relapsing-remitting MS but who have not yet begun treatment with any MS drug. CARE-MS II is scheduled to begin soon and will enroll patients who have continued to experience relapse episodes while on currently available disease-modifying therapies.

Initiation of this Phase 3 program follows the successful completion of the initial treatment period in the Phase 2 trial. Interim results from the Phase 2 trial indicated that alemtuzumab-treated patients experienced a statistically significant reduction compared with Rebif-treated patients in the risk for sustained accumulation of disability and the risk for relapse for 24 months. Results of the primary outcomes from this trial at 36 months are expected to be presented on Oct. 14 by Professor Alastair Compston during the Charcot Award lecture at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, in Prague.

The CARE-MS I study will enroll up to 525 patients at approximately 60 medical centers throughout North America, Australia, Latin America, and Europe, and will again compare alemtuzumab-treated patients to Rebif-treated patients according to two co-primary endpoints: the time to sustained accumulation of disability, and the annualized relapse rate. Alemtuzumab will be dosed at 12 mg/day for five days by daily IV infusion, with a second dosing 12 months later of 12 mg/day for three days. All patients will be followed from their entry into the trial until two years from the date that the last patient is randomized to treatment. Alemtuzumab-treated patients will continue to have safety evaluations for at least three years after the last course of treatment. The companies anticipate filing for marketing approval of alemtuzumab for the treatment of MS in 2011.

Alemtuzumab is an investigational drug for the treatment of MS and must not be used outside of a formal clinical trial setting in MS patients. Physicians or patients seeking additional information about the CARE-MS I trial should contact Genzyme Medical Information at 1-800-745-4447, option 2 in the United States, + 31 35 6991499 in Europe

About Alemtuzumab

Alemtuzumab is licensed in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. The product was launched in its oncology indication in 2001 in the US, where it is marketed by Bayer HealthCare Pharmaceuticals Inc. as Campath(R), and in Europe, where it is named MabCampath(R).

Alemtuzumab is a humanized monoclonal antibody that binds to a specific target, CD52, on cell surfaces and directs the body's immune system to destroy those cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-CLL.

Genzyme and Bayer Schering Pharma AG, Germany are co-developing alemtuzumab in oncology, multiple sclerosis and other indications. Bayer Schering Pharma AG, Germany holds exclusive worldwide marketing and distribution rights to alemtuzumab.

Campath has a boxed warning which includes information on cytopenias, infusion reactions, and infections. The most commonly reported adverse reactions in patients with B-CLL were infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

Source: Genzyme Corporation and Bayer Schering Pharma AG, Germany (26/09/07)

The Food and Drug Administration will allow Genzyme Corp. to continue human tests of a new multiple sclerosis drug that caused a fatal bleeding disease in one trial patient, the company said yesterday.

The drug, Campath , is a cancer treatment that has showed promise as a once-a-year infusion for multiple sclerosis patients.

Compared to a standard MS drug, Campath sharply reduced the number of disabling relapses suffered by patients in a clinical trial. But in 2005, Genzyme disclosed that one patient on Campath had died of bleeding in the brain. The Cambridge company voluntarily suspended its clinical testing of Campath and put a tight surveillance system in place to watch for symptoms of the bleeding disorder.

At a meeting of financial analysts in Boston yesterday, a Genyzme executive said the FDA had lifted the suspension. He said the clinical trial so far has yielded five other cases of the bleeding disorder, called immune thrombocytopenic purpura , or ITP. All of those patients were treated and recovered. With early detection and treatment, the problem amounts to a "manageable risk" for Campath patients, said the company.

Although the trial was effectively complete before the suspension, the lifting of the suspension allows Genzyme to move ahead in discussions with the FDA on two larger trials of Campath. Genzyme expects to launch those trials later this year.

Source: Boston.com © 2007 The New York Times Company (17/05/07)

Genzyme Corporation and Bayer HealthCare Pharmaceutical today announced detailed interim results from the CAMMS223 Phase 2 study. This interim analysis of all patient data through at least twenty-four months from the start of the study for all patients showed that a once-yearly cycle of alemtuzumab treatment had a statistically significant impact on reducing the frequency of relapses and the sustained accumulation of disability in early active relapsing remitting multiple sclerosis (RRMS) patients compared to Rebif® (interferon beta-1a).

The data were presented yesterday at the 59th Annual Meeting of the American Academy of Neurology (AAN) in Boston by Dr. Alasdair J. Coles, Ph.D., MRCP, Addenbrooke's Hospital, University of Cambridge, United Kingdom. This is the first time that an analysis of the primary and secondary endpoints has been presented in full.

Dr. Coles' presentation showed patients taking alemtuzumab at the high dose experienced an 87 percent reduction in the risk for relapse (p<0.0001) and a 66 percent reduction in the risk for progression of clinically significant disability (p<0.0098) when compared to patients treated with Rebif. At the low dose, patients taking alemtuzumab experienced similar results, with a 72 percent reduction in the risk for relapse (p<0.0001) and an 88 percent reduction in the risk for progression of clinically significant disability (p<0.0008) compared with patients treated with Rebif. Patients in both alemtuzumab arms also achieved a statistically significant reduction in disability compared with their pre-treatment baseline, as measured by their Extended Disability Status Scale (EDSS) scores.

"Although several therapies are already available to treat MS, patients still face an unmet need for more effective treatment that further stabilises disability," said Principal Investigator Professor D. Alastair S. Compston, MBBS, Ph.D., FRCP, FMedSci, Addenbrooke's Hospital, University of Cambridge, United Kingdom. "The large two-year reductions in the risk of relapse and sustained accumulation of disability seen in these interim results are impressive, and potentially very encouraging for the many people worldwide who currently face an uncertain future with this devastating disease and for their treating physicians."

As previously announced, dosing of alemtuzumab in this study was voluntarily suspended in September 2005 after three cases of immune thrombocytopenic purpura (ITP) were reported, the first of which resulted in a fatality. The U.S. Food and Drug Administration (FDA) subsequently placed the study on clinical hold. To date, six of the 216 (2.8 percent) alemtuzumab- treated patients in the CAMMS223 study have developed ITP. ITP is a disorder characterised by a low platelet count and corresponding increased risk of uncontrolled bleeding. Though potentially serious, ITP can be detected and monitored through blood tests, and is usually treatable.

At the time of the dosing suspension, most patients had received two cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm continued without interruption. Alemtuzumab re-dosing in the trial remains on clinical hold in the United States, and active discussions are underway with regulatory authorities regarding the clinical development program. Significant progress has been made toward the initiation of two planned Phase 3 clinical trials, one that will include previously untreated patients and one that will involve patients receiving an approved therapy whose disease remains active. These Phase 3 studies are expected to begin this year, following FDA clearance. Alemtuzumab is an investigational drug for the treatment of MS. Alemtuzumab should not be used in MS outside of the formal clinical trial setting so that patient safety, including the risk of ITP, can be monitored.

Phase 2 Study Details

The open-label, rater-blinded, randomised study enrolled 334 treatment- naïve patients with early, active, RRMS. The trial compares the safety and efficacy of alemtuzumab to Rebif. This is the first time that a potential new therapy for multiple sclerosis has undergone a prospective, controlled, multi- year, head-to-head comparison to a recommended first-line therapy.

In the trial, patients with RRMS at 49 medical centers in Europe and in the U.S. were treated with alemtuzumab at one of two doses (12 or 24 mg IV per day for five days at initial treatment, and for three days in the subsequent yearly treatments), or Rebif (44 mcg administered subcutaneously three times per week, as indicated in its product label). Although treating physicians were aware of which treatment patients received, independent (blinded) neurologists assessed the disability efficacy endpoint and performed relapse evaluations.

Primary endpoints in the trial were the annualised relapse rate and the time to Sustained Accumulation of Disability as measured by an increase in EDSS scores lasting at least six months. The efficacy and safety data analyses were reviewed by an independent Data and Safety Monitoring Board. The final analysis of the primary endpoints in CAMMS223 will be based on data through three years in all patients.

In addition to the results of the co-primary endpoints outlined above, Dr. Coles presented the interim results of the change from baseline in MRI T2 lesion volume and mean EDSS, which are secondary and tertiary endpoints, respectively. Each of these findings supports the results seen in the primary endpoints.

Safety Results

In the comparison of safety parameters of alemtuzumab vs. Rebif, a greater number of serious adverse events (a subset of total adverse events) were reported in patients receiving Rebif than in the two alemtuzumab dose groups combined. Most of these were associated with patients who were hospitalised for treatment of their MS.

The majority of adverse events (93 percent) in all three arms, including infusion-associated adverse events, were mild-to-moderate in intensity. The total number of adverse events was approximately twice as high in each of the alemtuzumab-treated arms as in the Rebif-treated arm, primarily due to the high number of infusion-associated adverse events. Excluding infusion- associated adverse events (i.e., those occurring within 48 hours of an infusion), the incidence of adverse events was similar across the three arms.

To date, a total of six of 216 (2.8 percent) alemtuzumab-treated patients in the CAMMS223 study have developed ITP. In the initial case, symptoms of ITP were experienced but not recognised in time to seek prompt medical attention. After that case, the sponsor notified investigators and patients of the risk of ITP, and a Patient Monitoring Program for ITP was implemented in CAMMS223. The other five ITP patients were diagnosed promptly, responded well to medical treatment, and have been stable without ongoing treatment for ITP for between five and thirteen months. No new cases of ITP have been reported in the study since September 2006. A presentation of updated ITP information will be made at the AAN conference by Herman Sullivan, MD on Wednesday, May 2, at 4:30PM EDT.

Additionally, the proportion of patients with thyroid-related clinical adverse events after alemtuzumab treatment was 16.2 percent vs. 1.9 percent after Rebif treatment. Thyroid adverse experiences were substantially less common in the two years after alemtuzumab treatment than in prior studies of the product in MS patients. A poster presentation of updated thyroid autoimmunity information will be made by Dr. Coles on Thursday, May 3.

About Alemtuzumab

Genzyme is conducting the clinical development program of alemtuzumab in multiple sclerosis. Bayer HealthCare holds exclusive worldwide marketing and distribution rights to alemtuzumab and participates with Genzyme in the design of clinical protocols and conduct of activities for the development of alemtuzumab for the treatment of MS. Alemtuzumab is an investigational drug for the treatment of MS, and should not be used outside of the formal clinical trial setting.

Alemtuzumab was approved in 2001 and is marketed outside the United States as MabCampath® and in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath®. The product is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the effectiveness of Campath is based on overall response rates. Comparative, randomised trials demonstrating increased survival or clinical benefit such as improvement in disease-related symptoms have not yet been conducted.

Alemtuzumab is a humanised monoclonal antibody that binds to a specific target, CD52, on some cells of the immune system, including lymphocytes. When alemtuzumab binds to these cells, it triggers their destruction by the immune system. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell Chronic Lymphocytic Leukemia (B-CLL), a malignant disease of B-lymphocytes.

Campath should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Campath has a boxed warning which includes events of hematologic toxicity, infusion reactions, and infections/opportunistic infections.

Campath is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type 1 hypersensitivity or anaphylactic reactions to Campath or to any one of its components.

The most commonly reported infusion-related adverse events in patients with B-CLL were rigors, drug-related fever, nausea, vomiting, and hypotension. Hematologic toxicities included pancytopenia/marrow hypoplasia, anemia, thrombocytopenia, neutropenia, and profound lymphopenia, and should be monitored. Infections reported included sepsis, pneumonia, and opportunistic infections such as CMV, candidiasis, aspergillosis, and mucormycosis.

Source: Genzyme Corporation (03/05/07)

As previously announced, dosing of alemtuzumab in this study was suspended in September 2005 after three patients developed immune thrombocytopenic purpura (ITP), a treatable condition in which patients experience a low platelet count as a result of an immune response directed against the platelets. At that time, most patients had received two cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm has continued without interruption. The trial remains on clinical hold in the United States, and Genzyme is working closely with clinical investigators and regulatory agencies to complete the study and ensure that the risk of ITP is well understood and managed. The company discourages physicians and patients from using alemtuzumab for MS outside of a clinical trial setting in which procedures are in place for managing ITP risk.

Efficacy Results

Analysis of the first co-primary endpoint showed that patients taking alemtuzumab at high and low doses experienced at least a 75 percent reduction in the risk for relapse after at least two years of follow up when compared to patients treated with interferon beta-1a. This difference was statistically significant in favor of the alemtuzumab patients at both high and low doses, with a p-value less than the pre-specified value (p=0.00328) assigned for the two-year interim analysis.

Analysis of the other co-primary endpoint showed that patients taking alemtuzumab at high and low doses experienced at least a 65 percent reduction in the risk for progression of clinically significant disability when compared to patients treated with interferon beta-1a. This difference was statistically significant in favor of the alemtuzumab patients at both high and low doses, with a p-value less than the pre-specified value (p=0.01194) assigned for the two-year interim analysis.

Results of additional secondary and tertiary efficacy endpoints, including MRI data, functional assessments, and quality of life measures, support the findings seen in the co-primary endpoints.

"These results continue to demonstrate that alemtuzumab has great potential to make a meaningful impact on the treatment of multiple sclerosis," said Richard A. Moscicki, MD, chief medical officer for Genzyme. "We will work with regulatory agencies in the United States and Europe, as well as our clinical investigators, to successfully complete this important trial and to prepare for the initiation of a Phase 3 trial in the first half of 2007."

Genzyme has requested a meeting with the U.S. Food and Drug Administration to present these data and to address the next steps in the development of alemtuzumab. The company has already received scientific advice from the European Medicines Agency for moving forward with a Phase 3 study.

Safety Results and Risk Management

Dosing of alemtuzumab in this study was suspended in the United States in September 2005 after three patients were diagnosed with ITP. The first patient to present with ITP died from the disease. Genzyme immediately implemented enhanced monitoring for ITP and has since created a comprehensive risk management plan to help physicians and patients participating in the trial detect ITP early and minimise the risk of complications. These efforts have been effective and have enabled the identification of all five additional patients with ITP symptoms. All patients requiring medical treatment for ITP have responded well. To date, a total of six patients have been diagnosed with ITP in this trial.

Other than ITP, serious adverse events related to treatment occurred among four patients treated with the low dose of alemtuzumab and four treated with the high dose. Two patients treated with interferon beta-1a experienced serious adverse events related to treatment. Common non-serious adverse events included infusion reactions in the alemtuzumab patients and flu-like symptoms in patients using interferon beta-1a. The incidence of all thyroid adverse events, including Graves' disease, was less than expected compared to reports in the literature on the use of Campath in MS. Safety information from the study related both to ITP and thyroid disorders will be presented in two weeks at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.

Phase 2 Trial Design

The phase 2 trial randomised 334 patients with active relapsing-remitting multiple sclerosis at 49 medical centers in Europe and the United States. Patients in the trial were treated with alemtuzumab at one of two doses (12 or 24/mg per day for five days at initial treatment, and three days of re-treatment), or interferon beta-1a (44 mcg administered three times per week, as indicated in its product label). The alemtuzumab regimen was administered once per year by intravenous infusion, while the interferon beta-1a regimen was administered three times per week by subcutaneous injection. The randomised trial compares the safety and efficacy of alemtuzumab with interferon beta-1a using two primary endpoints: the rate of relapse of MS symptoms, and the time to progression of clinically significant disability (time to Sustained Accumulated Disability over six months as measured by Expanded Disability Status Scale [EDSS]). Although treating physicians are aware of which treatment patients received, independent (blinded) neurologists assessed the disability efficacy endpoint.

About Campath

Campath (alemtuzumab), is indicated in the United States for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath continues to be available for its labeled indication in leukemia. Determination of the effectiveness of Campath is based on overall response rates. A randomised, controlled phase 3 trial demonstrating clinical benefits in previously untreated patients with B-CLL has been completed, and final safety and efficacy results have been submitted for presentation at a medical meeting later this year. Campath is a humanised monoclonal antibody that binds to a specific target, CD52, on cell surfaces directing the body's immune system to destroy malignant cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-CLL.

Genzyme is developing alemtuzumab in oncology, multiple sclerosis and other indications. Schering AG holds exclusive worldwide marketing and distribution rights to Campath. The product is marketed in the U.S. by Berlex Laboratories, a U.S. affiliate of Schering AG. Campath was launched in the U.S. in June 2001, and in Europe, where it is named MabCampath(R), in August 2001.

Source: PRNewswire-FirstCall (14/02/06)

Complications

A three-year trial comparing Campath (alemtuzumab) with Rebif (interferon beta-Ia) was temporarily suspended after one year when nine people taking Campath developed serious side effects according to a press release from manufacturers Genzyme Corporation and Schering AG Germany. Three people developed severe idiopathic thrombocytopenic purpura (ITP), a condition in which low levels of blood platelets can lead to abnormal bleeding. One person died of ITP and another person died of unknown causes. There also was one case of listeria meningitis (a serious infection of the membrane covering the brain and spinal cord) and two people developed Graves' disease, an autoimmune thyroid condition that requires lifetime maintenance. In fact, in earlier Campath studies involving people with MS, there was a 26% incidence of developing Graves' disease.

At the start of the trial, 334 people were randomly selected to receive either Campath as a one-time-a year, five-day IV infusion, or Rebif. Campath's developers reported that after one year, the 217 people receiving both high and low doses of Campath had 75% fewer relapses than were experienced by the group taking Rebif.

Wait and see

These are strong results. However, there won't be any further Campath treatments for MS until patient safety protocols are established. At present, Campath is used for the treatment of one type of leukemia. The companies emphasize that Campath should not be used for MS at this time. The study will continue to follow participants for a second year. We'll keep you posted on future developments.

Source: Inside MS Copyright National Multiple Sclerosis Society Feb/Mar 2006 (14/02/06)

The U.S. Food and Drug Administration issued a health alert on Wednesday over use of the drug in a clinical trial to treat multiple sclerosis, according Reuters.

Genzyme in September already suspended a clinical test after a patient died from abnormal bleeding and two others developed the condition. Genzyme remains in talks with the FDA about how to resume clinical trials that the company hoped to continue in the first half of 2006.

A Genzyme spokesman cited in the Reuters report said the alert may be intended for doctors who prescribe the treatment even though it isn't approved yet for MS.

Cambridge, Mass.-based Genzyme is jointly developing the drug with Germany's Schering AG. Campath has been approved since 2001 to treat leukemia but it carries a number of warnings relating to serious and potentially fatal side effects, including the condition that erupted during the multiple sclerosis study.

Source:  Boston Business Journal (01/12/05)

Shares in German drugmaker Schering fell as much as 1.1 percent on Thursday after U.S. regulators issued a health alert over its Campath drug in a trial to treat multiple sclerosis.

Campath is approved to treat a type of blood cancer, but in a study on multiple sclerosis, three patients developed a severe blood disorder and one of them died, the FDA said.

The company initially reported the serious side effect in September and put the trial on hold.

"This is the official posting on the FDA website that pertains exactly to the announcement we made in September. We are still in discussions with the FDA," said a Schering spokesman.

Analysts said the FDA warning was anticipated, but the focus would now be on the future of the drug to treat multiple sclerosis.

"This is the expected official warning," said MM Warburg analyst Ulrich Huwald. "It will now be interesting to see if Schering can go ahead with Phase III trials."

Another analyst, who declined to be named, said: "The FDA obviously wants to spell out the risks to doctors. It's now a challenge to Schering to minimize the risks in future trials so as to get a line extension for multiple sclerosis.

"It's difficult to say what impact it will have on the main use in blood cancer -- it will probably be small," he said.

In its alert, the FDA said patients should talk to their doctors if they were concerned about taking the drug. The agency added it had not reached a final conclusion about the trial's data.

The patients in question developed idiopathic thrombocytopenic purpura, a disorder that causes the body to attack its own platelets and is already mentioned on the drug's label. (07/12/05)

Three MS patients in Campath trial get blood disorder

Genzyme Corp. said yesterday that it has halted an experimental treatment for multiple sclerosis after three patients contracted a rare bleeding disorder and one of them died.

The company was testing Campath, a drug currently used to treat leukemia, on patients with multiple sclerosis.

Campath appeared to alleviate MS symptoms and showed signs that it might be able to halt long-term damage from the disease. But in some patients, it also triggered a dangerous drop in blood platelets, the cells that help the body clot and seal wounds.

Three of 219 MS patients given the drug were diagnosed with the blood condition, called idiopathic thrombocytopenic purpura. Genzyme said it will not give Campath to patients until the safety issue can be resolved.

''Multiple sclerosis is a very serious disease, and you don't want any deaths," Dr. Richard Moscicki, the Cambridge company's chief medical officer, said yesterday.

Moscicki said the patient who died had shown symptoms of the condition for a month without seeking medical care. The other two patients were diagnosed more quickly and are responding to treatment, he said.

Genzyme said it intends to continue testing the drug after working with regulators to improve the safety of the trials, but it will monitor patients more closely and instruct them to look for symptoms of the blood condition.

Campath is one of two cancer drugs Genzyme acquired last year when it bought Ilex Oncology Inc., a Texas company, for $1 billion. Ilex had already started the multiple sclerosis trial. Under the deal, Campath is owned by Genzyme but sold by the German drug company Schering AG.

The test was designed to measure the effectiveness of Campath in comparison with Rebif, a drug now on the market to treat MS symptoms, which can include numbness, vision problems, and disorientation.

After analyzing data from the first year of the planned three-year trial, Genzyme said patients on Campath were only one-quarter as likely to have a relapse of symptoms as those taking Rebif. It also showed some signs of slowing long-term damage, though not enough to be statistically significant.

Campath is approved only to treat a rare cancer called B-cell chronic lymphocytic leukemia. If it is approved to treat multiple sclerosis, sales could increase dramatically. The National Multiple Sclerosis Society estimates that approximately 400,000 people in the United States have MS.

An analyst said yesterday that the news was unlikely to have an immediate effect on the company's financial picture because Campath probably would not receive approval as an MS treatment before 2009.

''I think the data are intriguing because the efficacy seemed to be very strong," said Phil Nadeau, a biotechnology analyst for SG Cowen. ''It's now up to the company to better define the safety of the compound."

© Copyright 2005 Globe Newspaper Company.(17/12/05)

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