Three-Year Analysis Demonstrates Robust, Highly Statistically Significant Treatment Effect of Alemtuzumab Compared to Rebif
Genzyme Corporation today announced that top-line, three-year data from a completed Phase 2 clinical trial comparing alemtuzumab with RebifÂ® (interferon beta-1a) for the treatment of multiple sclerosis were presented this weekend at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague. The results come from an analysis conducted after 36 months of treatment for 334 patients in the three-year trial.
Results of the primary outcomes from this trial were presented by Alastair Compston, professor of neurology and the head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom, during the prestigious Charcot Award lecture at ECTRIMS.
Overall efficacy results demonstrate that alemtuzumab provides a significant treatment effect that has been found to last three years among patients in the study. Analysis of the first co-primary endpoint showed that patients taking alemtuzumab experienced at least a 73 percent reduction in the risk for relapse after three years of follow up when compared to patients treated with interferon beta-1a. This difference was highly statistically significant in favor of the alemtuzumab patients with a p-value less than the pre-specified value (p=0.00396) assigned for the three-year analysis.
Analysis of the other co-primary endpoint showed that patients taking alemtuzumab experienced at least a 70 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 with a p-value less than the pre-specified value (p=0.01646) assigned for the three-year analysis.
Results for the secondary endpoints support the findings seen in the co-primary endpoints. Full, detailed efficacy and safety data from the study are expected to be presented at the 60th Annual Meeting of the American Academy of Neurology next spring.
â€œThese results demonstrate the durability of the previously reported effect of alemtuzumab for the treatment of multiple sclerosis that, by our analysis, exceeds any current marketed products and anything that we can see in development,â€ said Richard A. Moscicki, MD, chief medical officer for Genzyme. â€œWe are very impressed with the consistency of these data and feel that they continue to point to the strong likelihood of alemtuzumab being approved for MS patients.â€
Safety Data: No New Cases of ITP
A total of six patients have been diagnosed with ITP associated with Grade 3 or 4 thrombocytopenia in this trial and there have been no new cases of ITP reported in the past year in this study.
Common non-serious adverse events included infusion reactions in the alemtuzumab patients and flu-like symptoms in patients using interferon beta-1a. Severe infections were infrequent in the alemtuzumab patients and were resolved with or without an intervention. The incidence of all thyroid adverse events, including Gravesâ€™ disease, was less than expected compared to early reports in the literature on the use of alemtuzumab in MS.
Two Phase 3 studies have recently begun examining the safety and efficacy of alemtuzumab for the treatment of multiple sclerosis. Genzyme and Bayer Schering Pharma AG, Germany announced last month the start of the CARE-MS I trial (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), a randomized, rater-blinded study that will compare alemtuzumab to RebifÂ® as first-line therapy for patients with relapsing-remitting multiple sclerosis (MS). The second Phase 3 study, CARE-MS II, also has begun and will enroll patients who have continued to experience relapse episodes while on currently available disease-modifying therapies.
Phase 2 Trial Design
The phase 2 trial randomized 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 intravenously for five days at initial treatment, and three days of re-treatment after 12 months with an option to treat again at 24 months), or interferon beta-1a (44 mcg administered by subcutaneous injection three times per week, as indicated in its product label).
The randomized trial compared the efficacy of alemtuzumab with interferon beta-1a using two primary endpoints: the rate of relapse of MS symptoms, and the time to Sustained Accumulation of Disability over six months as measured by Expanded Disability Status Scale [EDSS]. Efficacy assessments were made by independent neurologists blinded to therapy.
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 recently-initiated CARE-MS I Phase 3 trial should contact Genzyme Medical Information at 1-800-745-4447, option 2 in the United States, + 31 35 6991499 in Europe, or visit www.clinicaltrials.gov.
About Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic, debilitating disease in which the immune system attacks the personâ€™s brain and spinal cord. The disease causes a wide range of symptoms including fatigue, difficulty walking, numbness, and vision problems, and can progress to cause severe disability. Relapsing-remitting MS is the most common form of this disease.
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.
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 CampathÂ®, and in Europe, where it is named MabCampathÂ®.
Alemtuzumab is a humanized monoclonal antibody that binds to a specific target, CD52, on cell surfaces and directs the bodyâ€™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.
One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 9,500 employees in locations spanning the globe and 2006 revenues of $3.2 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation. In 2006 and 2007, Genzyme was selected by FORTUNE as one of the â€œ100 Best Companies to Work forâ€ in the United States.
With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious disease, and other areas of unmet medical need.
Genzyme Hosts Investor Call This Morning
Genzyme will host an investor call with Professor Alastair Compston this morning, Monday, October 15, from 8:30-9:30 a.m. EST. Three-year, top-line data from the Phase 2 study will be presented and there will be opportunity for investors to ask questions of the alemtuzumab investigator.
To participate in the call, please dial 1-888-889-4416 in the U.S. or 1-773-756-0616 outside of the U.S. The participant passcode is â€œGenzyme.â€
A replay of this call will be available by dialing 203-369-3276. This call will also be available live on the investor events section of www.genzyme.com.Â Replays of the call will be available until 9:29 p.m. on October 22, 2007.
This press release contains forward-looking statements, including statements about timelines for obtaining and presenting clinical trial data, the expected efficacy of alemtuzumab in MS and its comparison to current market products, the possibility of approval of alemtuzumab in MS, and the continued enrollment of patients in related MS clinical trials. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others, that actual results of the clinical trials demonstrate safety and efficacy comparable to the data that have emerged to date, the actual timing and content of submissions to and decisions made by the regulatory authorities, institutional review boards, data safety monitoring boards and treating physicians regarding the continued administration of alemtuzumab to MS patients, Genzymeâ€™s ability to develop and obtain approval of a patient safety plan, and the other risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Risk Factors" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of the Genzyme Quarterly Report on Form 10-Q for the quarter ending June 30, 2007. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements.