Genzyme Reports Interim Results from Trial of Campath® for Multiple Sclerosis
Date: September 14, 2006
Two-Year, Pre-Planned Interim Analysis Demonstrates Robust, Statistically Significant Treatment Effect of Campath Compared to Rebif®
Genzyme Corporation (Nasdaq: GENZ) today announced two-year interim results from a Phase 2 trial comparing Campath® (alemtuzumab) with Rebif® (interferon beta-1a) for the treatment of multiple sclerosis. The results derive from a pre-specified analysis conducted after two years of treatment for 334 patients in the planned three-year trial. This review was conducted in conjunction with an independent data and safety monitoring board.
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.
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 minimize 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 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 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 randomized 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 Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic, debilitating disease in which the immune system attacks the person'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.
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 randomized, 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 humanized 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®, in August 2001.
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. This year marks the 25th anniversary of Genzyme's founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,500 employees in locations spanning the globe and 2005 revenues of $2.7 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 more than 80 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 heart disease and other areas of unmet medical need.
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 and recommence alemtuzumab administration in the ongoing Phase 2 clinical trial in MS. 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 "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Quarterly Report on Form 10-Q for the quarter ended June 30, 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.
Genzyme and Campath® are registered trademarks of Genzyme Corporation. Rebif® is a registered trademark of Serono, Inc.