Wednesday, June 20, 2007
Genzyme and Bayer HealthCare Announce Detailed Interim Two-Year Alemtuzumab in Multiple Sclerosis Data Presented at AAN
Interim analysis of Phase 2 comparative study showed significant results in favor of alemtuzumab versus Rebif®
CAMBRIDGE, Mass. and Wayne, NJ - Genzyme Corporation (Nasdaq: GENZ) 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 stabilizes 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 characterized 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, randomized 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 annualized 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.
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 hospitalized 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 recognized 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 Multiple Sclerosis
Multiple sclerosis is an immune-mediated disease of the central nervous system (CNS) in which the immune system may attack the brain and spinal cord. MS affects approximately 2.5 million people worldwide and approximately twice as many women as men. The clinical course of MS is highly variable, but is typically characterized by an initial relapsing and remitting phase where episodes of transient neurological compromise are followed by partial to full recovery. Within 10 to 20 years, however, most patients experience progressive disability in which a steady worsening of symptoms may culminate in profound muscle weakness, impaired gait and mobility, bladder and bowel dysfunction, and cognitive and visual impairments. At onset, relapsing-remitting MS is the most common form of this disease.
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, randomized trials demonstrating increased survival or clinical benefit such as improvement in disease-related symptoms have not yet been conducted.
Alemtuzumab is a humanized 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.
Please refer to www.campath.com for complete prescribing information of Campath in CLL.
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 9,000 employees in locations spanning the globe and 2006 revenues of $3.2 billion. Genzyme has been selected by FORTUNE as one of the "100 Best Companies to Work for" 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 immune diseases, 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.
About Bayer HealthCare
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the US, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.
This press release contains forward-looking statements, including statements about clinical trial results, regulatory plans and expected timelines for alemtuzumab, including the initiation of a Phase 3 trial in MS patients and the timing thereof, and the ability to manage patient safety. 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 final results of the clinical trial demonstrate safety and efficacy comparable to the interim 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, Genzyme'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.
Please see the disclosure under the heading "Risk Factors" in the Management's Discussion and Analysis of Genzyme Corporation and Subsidiaries' Financial Condition and Results of Operations section of Genzyme's Annual Report on Form 10-K for the year ended December 31, 2006 for a more complete discussion of these and other risks. 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.
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
Genzyme®, Campath®, and MabCampath® are registered trademarks of Genzyme Corporation. All rights reserved.
Rebif® is a registered trademark of EMD Serono, Inc.
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