Adamas Pharmaceuticals reported that its Phase III INROADS trial of Gocovri (ADS-5102) for multiple sclerosis (MS) with walking impairment met its primary endpoint. That would seem to be good news, but the trial failed to meet secondary measures which worried investors, causing shares to drop by 45%.
Adamas Pharmaceuticals reported that its Phase III INROADS trial of Gocovri (ADS-5102) for multiple sclerosis (MS) with walking impairment met its primary endpoint. That would seem to be good news, but the trial failed to meet secondary measures which worried investors, causing shares to drop by 45%.
Gocovri was approved by the U.S. Food and Drug Administration (FDA) for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy. It is not approved for MS with walking impairment.
The primary endpoint of the study was a 20% improvement in walking speed from baseline to 12 weeks post-treatment. This was measured by the Timed 25 Foot Walk. The patients taking 274 mg of the drug had a statistically significant improvement in response rate of 21.1% compared to 11.3% in patients taking the placebo. At a lower dose of 137 mg, the response was 17.6%.
However, key secondary endpoints included mean change in the Timed 25-Foot Walk, the Timed Up and Go, and the 2-Minute Walk at 12-week post-treatment at both doses. The drug did not show a significant effect on any of those measures at either dose.
“We are pleased that ADS-5201 shows a potential benefit for MS patients with walking impairment, for whom there is a significant unmet medical need and limited treatment options,” said Neil F. McFarlane, Adamas’ chief executive officer. “However, as we did not see the scale of clinical benefit we had hoped for in this study we will fully assess the potential for ADS-5102 in MS patients before determining the extent of our continued investment in this program.”
The most common negative side effects were peripheral edema—swelling of the limbs, usually the legs—dry mouth, fall, constipation, urinary tract infections and insomnia. In the 275 mg group, 20.5% of patients discontinued the trial because of adverse events compared to 6.4% in the 137 mg group and 3.8% in the placebo group.
“Walking impairment negatively impacts many aspects of daily life for a large number of patients, and additional treatment options are needed,” said Jeffrey Cohen, INROADS Steering Committee Chair and director of experimental therapeutics at the Mellen Center for Multiple Sclerosis at Cleveland Clinic and a paid consultant for Adamas. “This trial result is encouraging for the MS patient and physician community and we look forward to reviewing the full data set.”
The company indicates it plans to analyze the full data set to further determine the efficacy and safety profile and dose-response. It is not currently planning to initiate a previously planned replicate second Phase III placebo-controlled trial. The company is continuing its open-label extension study and will launch discussions with the FDA to discuss a possible regulatory pathway.
MS is a chronic neurological autoimmune disease. The symptoms are often unpredictable. In the MS patients in the U.S., almost 270,000 have walking impairment. This is an area of high unmet need. There is currently only a single approved product on the market for the indication. It is Acorda Therapeutics’ Ampyra (dalfampridine).
