Ampyra Post-Marketing Study Results Announced - Low dose does not improve walking: Approved dose misses primary endpoint but shows benefit in several secondary endpoints
August 14, 2012
A post-marketing study of Ampyra® (dalfampradine-ER, Acorda Therapeutics) did not meet its primary endpoint, showing that a low dose (one-half of the approved dose) did not improve walking speed. The dose approved by the U.S. Food and Drug Administration (FDA) to improve walking in MS did not meet this endpoint in this study either, but did improve walking speed and endurance based on several secondary measures. These results were announced in a press release from Acorda dated August 13, which states that the company is presenting the information to the FDA (which required the study) and will present further details at future scientific meetings.
Background: Ampyra (10 mg, taken twice daily) is approved by the FDA to improve walking in people with MS, based on two studies which showed that walking ability improved significantly with Ampyra treatment. Because MS symptoms and the underlying disease pathology are both so variable, these studies first determined participants whose bodies responded to Ampyra using the Timed 25-Foot Walk (a measure commonly used to test walking speed), and then tested that population of responders.
As part of its approval, the FDA required Acorda to conduct a post-marketing trial testing a lower dose of Ampyra (5 mg, taken twice daily), compared with the 10-mg dose and inactive placebo. The FDA required that the study use the Timed 25-Foot Walk, without first determining responders.
Study Results: The Timed 25-Foot Walk did not improve significantly in either dose group compared to placebo. When investigators analyzed the data using methods similar to the previous studies, the 10-mg dose significantly improved walking speed compared with placebo in responders, but the 5-mg dose did not. In addition there were significantly more responders (average improvement in walking speed of at least 20% from baseline) in the 10-mg group compared to the placebo group. The 10-mg dose also improved walking endurance using the 6-Minute Walk Test; the 5-mg dose did not.
One person in the 10-mg group who had discontinued treatment four days previously lost consciousness, and a serious adverse event occurred in the 5-mg group as well, although details were not included in the press release. No seizures were reported, a possible side effect of Ampyra. Other adverse events associated with Ampyra included urinary tract infection, nausea, dizziness, insomnia and upper respiratory tract infection.
The company is presenting the results of this required study to the FDA. If the agency requires changes to prescribing recommendations, the National MS Society will inform the MS community as quickly as possible.
Ampyra is a registered trademarn of Acorda Therapeutics.