Pfizer’s tafamidis program for Transthyretin Familial Amyloid Polyneuropathy (acquired via the buyout of FoldRx) has reached the FDA, and the CNS Advisory Committee charged with assessing tafamidis in the treatment of this rare disease has made an equally rare, and bold foray into a revamping of pivotal trial standards. After ruling that the standard clinical endpoint data, the primary endpoint measures of disease progression and quality of life, were not sufficient for approval, the Committee voted 13-4 that the surrogate endpoint data from Phase III testing would be, provided Phase IV testing be added to support the claim of clinical benefit. The three surrogate measures cited were all secondary endpoints in Phase III; muscle strength, small fiber function, and a biomarker, TTR protein stability.
This could be a huge precedent. Given the immense challenges, particularly the time required, associated with confirming impact on disease progression, the process of having to do so prior to drug approval mandates enormously expensive and slow Phase III testing. NIR believes strongly that changes in specific functional measures and biomarkers may prove to be equally useful predictors in other neurodegenerative disorders, including Alzheimer’s and Parkinson’s. Indeed, this is a major component of a legislative initiative being prepared by the Neurotechnology Industry Organization, and the FDA’s AC move in this direction is a sign of where the regulatory process must move eventually, and the sooner, the better.
Now the submission is in the hands of the FDA, with a PDUFA date of June 16. If approved on this basis, the FDA will take a major step towards facilitating the development and availability of disease-modifying neurotherapeutics. If they do not accept the AC’s recommendation, that would be an indication that their public statements regarding improvements in the regulatory environment constitute insincere posturing. We will know soon enough.