Accelerate Approval Pathway Does Not Need Reform, But Enforcement and Education
(Thursday, August 26, 2021)
Since the approval of the Alzheimer’s Drug, Adulhelm, almost three months ago, the accelerated approval pathway (AAP) has been criticized, to a large extent, unfairly. The criticism misses the lax enforcement of the well-established rules for the pathway by the FDA for such decisions. The AAP requires demonstration of benefits of a new drug in terms of scientifically sound surrogate endpoints. This evidence must be generated in prospectively planned controlled clinical trials and must be clear and indicative of the claimed benefit for the target disease. In Aduhelm’s case, this was not true. Not only was the data inconclusive, but the scientific validity of the surrogate endpoint was also highly questionable. An independent review of the clinical trial data by the Advisory Committee saw major issues with the data. FDA’s management should have looked at the data and pushed back to the developers to generate further data. But instead, FDA took the scientifically questionable approach of approving the product despite lack of credible evidence considering no treatment options for patients. Giving patients false hope is not FDA’s intent but that’s exactly what it did. The fact that FDA suggested the AAP to the sponsor as a remedy for a program in quagmire has been erroneously reported in the media as improper. Lost is the point that despite that, the drug did not even meet its surrogate endpoint in the clinical trials. In the process, FDA created a precedence that would be used by others to similarly push unacceptable data for approval. And this is the second time in recent years that FDA did this, ruining the credibility of the AAP. So, it is FDA that needs more discipline not the pathway that needs reform. The intent of the AAP was to create a faster pathway for promising products and mostly it has done the job. Of the 269 products approved via the AAP, less than 5% were controversial decisions. FDA needs to defend the AAP by enforcing its own rules for selecting scientifically sound surrogate endpoints, apply similar review standard to all applications, and enforce post-market commitments. It also needs to educate the general public about AAP to build trust in the pathway. This regulatory pathway has served well in providing numerous treatments over the last 25+ years to diseases such as AIDS and cancers that could still have been untreated if not for AAP. FDA leaders now need to control the process to avoid discrediting the pathway.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC