Is FDA’s Accelerated Approval Pathway in Danger of Being Scrapped?
(Thursday, August 5, 2021)
A review published in the British Medical Journal this week reported that almost 44% of drugs approved by the FDA under the accelerated approval pathway over the last 28 years have not yet been confirmed to be clinically effective, and despite that most of these unconfirmed drugs are on the US market for 5 years or more, with some for almost 20 years. With the highly controversial Aduhelm approval a few weeks back, the accelerated program is under intense public scrutiny. FDA has strongly pushed back against the critiques of the pathway claiming that it has led to good treatments for several indications, particularly for rare diseases. But publicly available data says otherwise. Many of the manufacturers of the 112 drugs in question have not even finalized the clinical protocols for the studies they were required to conduct as a post-market commitment. Obviously, the manufacturers do not feel much pressure to rush their studies and are able to use the regulatory processes to delay their studies. Once approved, the threshold for the market withdrawal is set so high that only 16 drugs out of 253 approved under the accelerate approval pathway were withdrawn from the market, mostly voluntarily by the manufacturers. All this while, these drugs made billions of dollars for their owners. That said, so far there is strong support at the FDA and in the political circles for the accelerated approval pathway. The accelerated approval pathway helped with combating the AIDS epidemic and numerous cancer drugs. The biggest hurdle is FDA’s enforcement of the post-market commitments, as is obvious from the record. For the companies selling these products, post-market studies are also harder since most patients would rather buy the FDA-approved drug than participate in a clinical trial for the same drug. Regarding the hoopla, expect the following: First, the accelerated approval pathway is here to stay; all indications are that neither the FDA or Congress has the desire to make significant changes to the program. There are sufficient positive reasons to keep this pathway for it to be derailed with one event. Second, expect stronger enforcement by the FDA of the post-market commitments. FDA, it seems, is not as assertive as one would expect about holding the manufacturers accountable for post-market studies. It is not reasonable that 5 or more years are spent in finalizing a clinical protocol. The recruitment rates and data generation from the clinical studies are hard to predict but there should be stronger efforts from FDA to ask sponsors to communicate progress reports on the post-market studies and to troubleshoot in a timely manner. Third, the Aduhelm case is likely a distraction from the bigger question of the use of the accelerated pathway. It does not seem that anyone at FDA did anything improper or illegal during the review of Aduhelm clinical development program or approval decision. Companies looking to use the accelerated approval pathway should not get discouraged by the media hype and continue with their efforts to pursue the regulatory pathway best suited for their product(s). There is no risk to the accelerated approval pathway despite what the news may convey.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC