While the roster of 48 drugs (plus 4 notable biologics) the FDA approved in 2019 didn’t break any records with the sheer number it was remarkable in one aspect: The agency reached deep into a group of therapies they didn’t need to make a decision on until later this year, in some cases speeding drugs up by months ahead of even priority review deadlines.
On the surface, that’s great news for drugmakers and the patients they hope to help. But according to a recent study on rushed approvals, it could also spell safety troubles down the road.
Back in July, a trio of economists at NBER crunched the data on drugs OK’d before supposed deadlines such as the end of months, years or before holidays and found that treatments approved under these apparent “desk-clearing” efforts — in which regulators felt the pressure of informal performance benchmarks — are more likely to be associated with postmarket safety issues.
“We see about twice as many adverse effects,” Lauren Cohen, a professor of finance and entrepreneurial management at Harvard Business School and one of the authors, told the Wall Street Journal.
Cohen and his colleagues, Umit Gurun of the University of Texas at Dallas and Danielle Li of MIT, considered only the surge of approvals in December, at the end of each month and before holidays such as Thanksgiving.
In 2019 seven out of 48 novel chemical entities were approved in December, largely in line with the 15% proportion that the researchers noted in previous years. But notably, 21 OKs came through in Q4, accounting for 43% of the whole crop.
FDA spokesperson Nathan Arnold acknowledged the December jump pattern but told the Journal that its share has actually diminished from the 1980s.
“While we cannot speak directly to the results on informal deadlines highlighted in this study, FDA has—on multiple occasions—investigated a closely related issue, which is the relationship between formal PDUFA deadlines and postmarket safety of drugs,” Arnold added. “We have not found evidence of such a relationship.”
Drugs that appeared to have been approved with little heed of the PDUFA deadlines might be another issue. Vertex’s Trikafta (for cystic fibrosis), BeiGene’s Brukinsa (for mantle cell lymphoma), Novartis’ Adakveo and Global Blood Therapeutics’ Oxbryta (for sickle cell disease), as well as Alnylam’s Givlaari (for acute hepatic porphyria ) and AstraZeneca/Daiichi Sankyo’s Enhertu (for HER+ breast cancer) all belonged to that group.
Cohen, Gurun and Li prescribed a solution for the safety concerns they spotted:
A potential policy response to the patterns we document is to more carefully scrutinize drugs that are approved during such output surges. Regulators could, for instance, review end-of-year decisions in the following year before providing an ultimate approval (or lack thereof).