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Thursday, September 14, 2006

Genzyme Shows Its MS Treatment Is Superior to Serono's Rebif

This morning Genzyme (GENZ) released its phase II multiple sclerosis MS drug study results. These results are interim after a two-year period, but the study was designed to compare its Campath ® to Serono’s (SRA) Rebif®. It monitored 334 patients in the planned three-year trial, and this was in conjunction with an independent data and safety monitoring board.

It was already announced, but they halted dosing in September 2005 after 3 patients developed low platelet counts from an immune response and one of the patients had died. Treatment with Rebif® continued in the control arm without interruption. The trial remains on hold in the US and Genzyme is working to complete the study.

Rebif® is co-marketed in the US by Serono (SRA) and Pfizer (PFE). Serono has said in filings that full global Rebif sales were $1.2698 Billion for 2005, approximately half of Serono’s sales.

This signals that the company does plan to go into a Phase III and ultimately with a new drug application at the FDA. The most important quote from the long data provided is as follows: "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."

Shares of GENZ are trading up 1.1% pre-market at $67.31. Shares of SRA have not yet traded in the US, but shares of PFE are trading down 0.25% pre-market at $28.11.

Here are the Efficacy statements from the company:

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.
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