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Developers have increasingly relied on an FDA shortcut to win accelerated drug approvals while their confirmatory trials got delayed at the expense of billions of dollars to the government-backed healthcare system, a recent analysis from Bloomberg News indicates.
The FDA’s accelerated approval program, which became law in 2012, allowing the FDA to greenlight medicines on early trial results, is intended to help drugmakers to develop treatments for unmet medical needs.
Over the past three decades, about 300 marketing applications, mainly for cancer drugs, have been cleared under the accelerated program after regulators first introduced it in 1992, partly to speed up the market entry of HIV drugs.
In approving drugs under the accelerated path, FDA regulators use surrogate endpoints such as radiographic images and physical signs that are believed to predict a drug’s clinical benefit,
However, for the continuation of approvals, the developers are required to conduct confirmatory clinical trials to prove their direct clinical benefit. At the same time, those partially proven drugs can stay on the market, generating, in some cases, billions of dollars in sales for developers even as their confirmatory trials get delayed.
The agency’s accelerated approvals peaked in 2020 with 47 such approvals before declining to 25 and 15 in 2021 and 2022, respectively, as the program sparked controversy when the FDA used it to clear drugs aimed at challenging areas in medicine.
In 2021, the FDA went against the recommendation of its independent experts to clear Aduhelm, the Alzheimer’s therapy developed by Biogen (BIIB) and Eisai (OTCPK:ESALF) (OTCPK:ESAIY), under the accelerated path.
In the wake of that decision, the Office of Inspector General at the Department of Health and Human Service found the burden of drugs cleared under accelerated approvals but whose confirmatory trials got delayed by at least six months. According to HHS-OIG, drugs with accelerated approvals and delayed confirmatory trials cost $18B for Medicare and Medicaid during 2018 – 2021.
According to the Bloomberg analysis, confirmatory studies for 19 drugs with accelerated approval were yet to complete as of April, meaning the trials were behind schedule or moved past their official due dates. There were seven other drugs for which developers had submitted some clinical data to the FDA and therefore were not categorized as those with delayed confirmatory trials.
Against this backdrop, the FDA is taking a firm stand on accelerated approvals where confirmatory clinical studies remained unfinished or failed.
This year, two hurriedly approved drugs, including Switzerland-based Covis Pharma’s preterm birth drug Makena have been pulled from the market. Following a lengthy regulatory battle, Covis, backed by Apollo Global Management (APO), withdrew Makena from the market in March after more than a decade since its accelerated approval.
According to the Bloomberg analysis, the loss of accelerated approvals peaked in 2021 and 2022, with the exit of seven such drugs each year.
Accelerated pathway has also helped pharma majors such as Merck (NYSE:MRK), Bristol Myers Squibb (NYSE:BMY), AbbVie (NYSE:ABBV), and Johnson & Johnson (JNJ) to sustain blockbuster status for some of their cancer drugs.
HHS-OIG findings indicate that Imbruvica, developed by AbbVie (ABBV) and Johnson & Johnson (JNJ), has led to $707M in Medicare and Medicaid spending during 2018 – 2021 even as certain confirmatory trials for the blood cancer drug remained delayed. Meanwhile, anti-PD-1 immunotherapy Opdivo from Bristo Myers (BMY) has cost $631M for Medicare and Medicaid during the period.
The business models of some drugmakers are entirely reliant on accelerated approvals. Sarepta Therapeutics (NASDAQ:SRPT) won FDA accelerated approval for all three drugs in its portfolio, bringing $2.5B in sales over the years from patients with Duchenne muscular dystrophy.
The biotech focused on RNA-targeted therapies has yet to complete the confirmatory study for Exondys 51, its first to receive accelerated approval in 2016, and the company’s two other drugs. Exondys 51 has cost Medicare and Medicaid $674M in 2018 – 2021, as its confirmatory trial did not get started even four years after its approval.
Since then, the FDA has got more teeth for its accelerated approval program. In December, Congress passed legislation that, among other things, required developers to have confirmatory clinical trials underway at the time of approval.
Sarepta (SRPT) attributes its delays for the Exondys 51 program to various factors, including some requirements laid out by the FDA. The company aims to complete a confirmatory study for Exondys in 2024 and for its two other drugs a year later.
Meanwhile, thanks to the accelerated approvals, Sarepta (SRPT) is also expanding its gene therapy program, which according to chief executive Douglas Ingram, “wouldn’t have existed without the Exondys approval.”
By May 29, the biotech is poised to win the FDA nod for its Roche (OTCQX:RHHBY) (OTCQX:RHHBF)-partnered Duchenne gene therapy SRP-9001 after an FDA advisory panel backed its accelerated approval about a week ago.
