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Title: Alemtuzumab Reduces Relapses, Prevents Accumulation of Disability Compared With Standard Therapy: Presented at ECTRIMS

"Alemtuzumab Reduces Relapses, Prevents Accumulation of Disability Compared With Standard Therapy: Presented at ECTRIMS"

By Chris Berrie PRAGUE, CZECH REPUBLIC -- October 17, 2007 -- Early treatment with alemtuzumab -- a humanized monoclonal antibody against the CD52 antigen -- shows significantly greater improvements in disability for up to 3 years and delays the time to first relapse when compared with standard treatment with interferon beta-1a (IFNbeta-1a) in patients with relapsing-remitting multiple sclerosis (RRMS). These findings are from two studies presented here at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The CD52 antigen is expressed at high levels on lymphocytes, so alemtuzumab treatment causes a rapid depletion of T cells, B cells and natural killer cells -- cell types that are implicated in the pathogenesis of MS. In a presentation on October 13, Alasdair J. Coles, MD, PhD, University Lecturer, Cambridge University School of Clinical Medicine, Cambridge, United Kingdom, presented the 2-year results from the Campath-1H in Multiple Sclerosis (CAMMS223), an international, multicenter, randomized, assessor-blind, phase 2 trial. In CAMMS-223, researchers randomized 334 patients with RRMS to IFNbeta-1a 44 mcg SC 3 times weekly or to alemtuzumab at either a low dose (12 mg/day IV daily for 5 days) or at a high dose (24 mg/day IV daily for 5 days). Some patients in the study also received further alemtuzumab daily for 3 days at month 24, as specified by the original trial design, although this was modified due to safety concerns, and approximately 80% of patients did not receive this dosing at month 24. All patients also received 3 days of methylprednisone IV at months 0, 12 and 24. These previously presented 2-year results showed significantly greater improvements by both doses of alemtuzumab ([P =.0219; P =.0010) in MS functional composite z scores over those seen for IFNbeta-1a.

Similarly, alemtuzumab provided significant benefits over IFNbeta-1a in the time to first relapse at 2 years, with reductions in the risk for relapse of 70% with the low dose (P <.0001) and 83% with the high dose (P <.0001).

"If you give this aggressive lymphocyte-deleting antibody early in the course of MS, then it has a fantastic efficacy in terms of reducing relapses, preventing the accumulation of disability, compared not to placebo, but compared to the interferon, the standard licensed therapy," Dr. Coles said.

In another presentation at ECTRIMS, Alastair Compston, PhD, Professor of Neurology and Head, Department of Clinical Neurosciences, University of Cambridge, Cambridge, U.K., provided the final, 3-year, results from CAMS223.

In the final year of the CAMMS223 trial, some safety concerns became apparent, Dr. Compston said during his Charcot Award Lecture on October 14. These arose due to development of autoimmune disease during the use of alemtuzumab, and involved six cases of idiopathic thrombocytopenic purpura, along with secondary thyroid autoimmunity. Furthermore, the first of these patients died prior to reporting the problem, although the remaining five were rescued, he said.

Although it can be potentially serious, idiopathic thrombocytopenic purpura can be detected and monitored through blood tests, and is usually treatable with several drugs, such as prednisone and other immunomodulatory therapies.

On this basis, the third and final alemtuzumab treatment, due at month 24, was cancelled in approximately 80% of study subjects. This meant that at the 3-year assessment, many of the patients had seen no further treatment since the second treatment at month 24, Dr. Compston stressed.

Despite this fact, the efficacy of alemtuzumab in comparison with IFNbeta-1a continued to be high, he noted.

Following from the significant 80% reduction in the risk of relapse with the combined low- and high-dose alemtuzumab over IFNb-1a at year 2, at 3 years, this was almost totally maintained, despite no further medication, at 73%.

Similarly, the significant 74% decrease in the risk for progression of clinically significant disability at 2 years was maintained (71%) at 3 years, confirming again the benefits associated with alemtuzumab for patients with RRMS.

Thus, Dr. Compston summarized the main benefits seen in the CAMMS223 trial as: (1) alemtuzumab is significantly more effective than high-dose IFNbeta-1a at suppressing relapses and slowing accumulation of disability; (2) disability increases over time with IFNbeta-1a treatment, while it improves with alemtuzumab; (3) no clear dose response can be demonstrated; (4) the outcomes appear to be improved after three cycles of treatment; and (5) the main adverse effects are secondary autoimmunity.

"So the important message is, if you take alemtuzumab, [3] years later, your disability is [still] less than it was at the outset, so patients coming onto our trial actually improve if they take alemtuzumab," Dr. Compston said.

"We would hope that this will become a treatment for people who have early MS with signs of an aggressive disease but who aren't disabled, so we could prevent them getting disabled," he added.

Funding for these studies was provided by Bayer Schering Pharma and by Genzyme Corporation.

[Presentation titles: Alemtuzumab Improved Multiple Sclerosis Functional Composite Scores and Delayed Time to First Relapse at 2-Year Interim Analysis Compared to Subcutaneous Interferon Beta-1a. Abstract P557; A Peculiar Lesion in the Cord With Atrophy - Is Multiple Sclerosis an Inflammatory or Neurodegenerative Disease? Charcot Award Lecture. Abstract 128]

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