I've also posted this under the Campath thread
Genzyme Reports Interim Results From Trial of Campath(R) for Multiple Sclerosis
Genzyme Corporation today announced two-year interim results from a Phase 2 trial comparing Campath(R) (alemtuzumab) with Rebif(R) (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 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.
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.