Apr 15, 2008

Disappointing Results from Trial of Rituximab in Primary-Progressive MS

Drug did not achieve primary goal of slowing progression, sponsors still analyzing other outcomes

A study of intravenous rituximab (Rituxan®, Genentech and Biogen Idec) in 439 people with primary-progressive MS* has shown that the drug did not slow disease progression when compared with inactive placebo, the primary endpoint of the study. These results have been announced in a press release from Genentech and Biogen Idec dated April 14, 2008. The companies say that they will continue to analyze the data and will present the results at an upcoming medical meeting.

Background:

Rituximab binds to a molecule (CD20) on the surface of B cells and depletes them from the circulation for an average of 9 months. B cells are immune cells that make antibodies and may play a role in the immune attack on brain and spinal cord tissues in multiple sclerosis. Rituximab is approved for treating some forms of cancer. Researchers reported earlier this year that in aphase 2 study, one intravenous course of rituximab reduced disease activity and relapses for 48 weeks in people with relapsing-remitting MS** (The New England Journal of Medicine2008 Feb 14;358[7]:676-88). The current study evaluated the safety and effectiveness of rituximab in people with primary-progressive MS, a course of MS for which no treatments are currently on the market.

The Study:

The study enrolled 439 subjects at 60 sites in the United States and Canada. Participants were age 18-65 years, had primary-progressive MS, and had had MS for at least one year. Patients were randomly assigned to receive either four intravenous doses of Rituxan or inactive placebo every six months for 96 weeks. MRI evaluations were conducted before treatment, and at weeks 6, 48, 96 and 122. The primary outcome measured was the time to confirmed disease progression.

Results:

Rituximab did not reduce the time to disease progression, as compared with placebo. In the press release, Hal Barron, MD, Genentech senior vice president, development and chief medical officer, notes, "There was some evidence of biologic activity, and we will continue to review all the data to better understand the role of B cells in MS."

The safety data from the study are still being analyzed as well. Serious adverse events occurred more often (16.4%) in the rituximab arm than in the placebo group (13.6%), with serious infections occurring more often in the rituximab group (4.5% vs. less than 1%) as well. There were more infusion-related reactions with rituximab, mostly mild to moderate in severity.

“This announcement is disappointing to be sure,” said John R. Richert, MD, executive vice president for research and clinical programs at the National MS Society. “It highlights the urgent need for more focused research to understand and uncover therapeutic targets for the progressive phases of MS and to develop better tools to assess brain and spinal cord tissues to help track the effectiveness of therapies. We're grateful that Genentech and Biogen Idec conducted this study in the underserved patient population with primary-progressive MS.”

Read more about ongoingresearch on progressive MS, and aboutliving with primary-progressiveand other progressive courses of MS.

*Primary-progressive MS is a course of MS characterized by a slow but nearly continuous worsening of disease from the onset.**Relapsing-Remitting MS is a course of MS characterized by clearly defined flare-ups followed by partial or complete recovery periods (remissions) free of disease progression between attacks.

Rituxan is a registered trademark of Genentech and Biogen Idec