Expanding the Scope of Acceptable Endpoints in Accelerated Approval

Last week in my blog I touched on Recommendation 1 from PPMD’s white paper. Today, I wanted to take a minute to examine Recommendation 2 and why it is a critical part of Putting Patients First: Recommendations to speed responsible access to new therapies for Duchenne muscular dystrophy and other rare, serious and life-threatening neurologic disorders.


Recommendation 2: The FDA should expand the scope of acceptable endpoints, including novel surrogate and intermediate clinical endpoints, used to approve drugs for serious or life-threatening diseases with unmet medical need.


The 6 Minute Walk Test (6mwt) 

PTC Therapeutics was the first to use the 6mwt as the primary outcome in the Ataluren trials. From that study (and thanks to PTC for sharing their data), we have learned that parameters exist (250-400m/6m) for using the 6mwt as a primary outcome, suggesting that boys who walk <250meters in 6 minutes have a greater risk of losing ambulation during a 48-week study. Likewise, boys walking >350-400m in 6 minutes are likely to be stable during a 48-week study.  


And while both FDA and industry are becoming more comfortable with the 6mwt, reliance on this sole endpoint necessarily excludes a significant proportion of patients affected by Duchenne from participation in trials, i.e. very young patients and patients already confined to a wheelchair are unable to participate in the trial. In addition, the relatively long-time horizon over which Duchenne patients experience progressive functional decline requires lengthy clinical trials. 


For this reason, researchers and industry are exploring the use of biomarkers, such as imaging tests, pulmonary function tests, and dystrophin levels as surrogate endpoints.

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