Jul 29, 2009
Disappointing Results from Phase 3 Clinical Trial of Dirucotide (MBP8298) in Secondary-Progressive MS -- Companies announce halt to ongoing trials of dirucotide in MS
Intravenous dirucotide (MBP8298, BioMS Medical Corp.) did not delay disease progression significantly more than inactive placebo – the primary endpoint of a two-year, phase 3 study in 612 people with secondary-progressive MS, according to a company press release. The company and partner Eli Lilly & Company are continuing to analyze data from the study, also known as the MAESTRO-01 study. The companies are discontinuing two other studies of this experimental compound in people with secondary-progressive MS (MAESTRO-02 and MAESTRO-03), and they recommend that study participants contact their investigators if they have questions.
Background: Dirucotide (also known as MBP8298) is a synthetic fragment of myelin basic protein (MBP, a component of myelin), which reduces the production of spinal fluid antibodies that react against MBP during the immune attack on the brain and spinal cord that occurs in MS. An earlier phase 2 study of dirucotide showed a statistically significant delay in clinical progression among individuals with certain genetically determined “HLA” types; HLA is a molecular tag located on body cells that helps the immune system attack foreign invaders and, in the case of autoimmune diseases, the body’s own tissues. Disappointing results from a phase 2 trial of dirucotide in relapsing-remitting MS were announced by the companies in February 2009.
Secondary-progressive multiple sclerosis is a stage of the disease that follows an initial period of relapsing-remitting MS in many people. In secondary-progressive MS, the disease worsens steadily, with or without occasional flare-ups, minor recoveries or plateaus.
The Study: A total of 612 people with secondary-progressive MS who possessed specific HLA immune response genes were recruited in Canada and Europe and randomly assigned to receive intravenous dirucotide or inactive placebo every six months for two years. The primary endpoint was increase in the time to disease progression, as measured by the EDSS (Expanded Disability Status Scale). Results suggest that dirucotide did not significantly reduce disease progression, and also did not meet secondary endpoints.
The companies announced that they are discontinuing two other ongoing trials in people with secondary-progressive MS, including MAESTRO-02 and MAESTRO-03, and evaluate data from these studies gathered to date. MAESTRO-02 is an open-label study of people who finished MAESTRO-01, and MAESTRO-03 is a phase 3 trial involving 510 people with secondary-progressive MS in the U.S. The companies are informing regulatory agencies and providing instructions to investigators outlining the process for discontinuing the studies. Study participants who have questions should contact their study investigators.
Comment: “We are very disappointed that this study was negative, given the significant unmet need for better treatment options for people with secondary-progressive MS,” said John R. Richert, MD, Executive Vice President of Research & Clinical Programs at the National MS Society. “Hopefully analysis of the full results will offer valuable clues to new approaches to treat the progressive stages of MS.”