[Opinion Piece] New Alzheimer’s drug is a problem for FDA’s pass-fail approach
[Opinion Piece] New Alzheimer’s drug is a problem for FDA’s pass-fail approach
This is an op-ed written by Jerry Avorn. His bio from WaPo:
Jerry Avorn is a professor of medicine at Harvard Medical School and co-director of the Program on Regulation, Therapeutics and Law (PORTAL) at Brigham and Women’s Hospital in Boston.
The author argues that the accelerated approval process within the FDA has led to drugs reaching the market that fail to show efficacy when administered more widely. They write:
For these medicines, the FDA has granted “accelerated approval” based not on patients’ clinical improvement but merely on small changes in lab tests. After accelerated approval, drugmakers are asked to do follow-up studies to prove that their drugs actually help patients. But the government may allow many years to complete such studies, and they are often started late or done poorly, my research group has found.
As an example of the accelerated approval process gone wrong the author points to Makena:
In 2011, a medication meant to prevent premature birth, Makena, was approved on an accelerated basis, but then was never clearly shown to work. Getting it off the market took until this past April.
The author proposes a middle-ground between the pass/fail status that the FDA gives medicines currently:
The FDA’s simple all-or-none decision framework is a poor fit for this evolving scientific reality. The agency should instead create a new status for some drugs that is neither full approval nor outright rejection — a conditional approval that would allow a new drug with ambiguous credentials to be used only in a limited way until better evidence is collected.
In my professional life, I have worked on a number of clinical phase therapeutics and authored sections of regulatory filings submitted to agencies like the FDA and EMA. Several of those assets were classified as orphan drugs and were granted accelerated approval. I think that the accelerated approval process fulfills a role that is needed in cases where there is an unmet medical need. Additionally, some indications lend themselves to proven proxy measures for efficacy that give a high level of confidence in clinical use. However, the accelerated approval process as it is currently used is prone to abuse in that the FDA is not able or willing (not sure which) to enforce post-approval actions on drugmakers in a timely fashion.
The author's example of Makena shows that over a decade can pass without showing medical efficacy in follow-up trials before marketing authorization is pulled. The author doesn't go into detail, merely linked to it, but the conditional approval granted by the EMA is much more fit for purpose. Under that process, the conditional approval is just granted for one year and must be renewed each year. I have not worked on this renewal process personally, but from experience interacting with the agencies before, they would be looking for material progress towards meeting any stated post-approval obligations. This process gives the EMA an annual chance to pull a product if there is ambiguous or no demonstrated clinical effect or if the adverse events are more severe or common than anticipated.
As an aside, I found it interesting that the impending Leqembi (lecanemab) accelerated approval is what inspired this article. Leqembi's predecessor, Aduhelm (aducanumab), was granted accelerated approval, but was so poorly received by the market/hcp's/insurance companies, that it might as well have not been approved at all.
Totally agree. It's so tough to be on the clinical side too, and have drugs with really marginal data get approved and then have to counsel patients and families on them. FDA needs to enforce the companies actually gathering definitive efficacy data in a timely manner if they want to stay on the market. Especially at the eye watering prices they are often charging for new therapeutics that often have no good relation to the value they're actually supposedly bringing.