Developers have increasingly relied on an FDA shortcut to get fast-track drug approvals while their confirmatory trials have been delayed at the expense of billions of dollars for the government-backed healthcare system, a recent analysis of Bloomberg News noted.
The FDA’s Accelerated Approval Program, which which became law in 2012, allowing the FDA to greenlight drugs on early trial results, is intended to help drugmakers develop treatments for unmet medical needs.
Over the past three decades, about 300 marketing applications, mostly for cancer drugs, have been approved under the fast-track program after regulators first introduced it in 1992, in part to speed up the process. entry into the HIV drug market.
When approving drugs under the fast track, FDA regulators use surrogate endpoints such as x-ray images and physical signs that are believed to predict a drug’s clinical benefit,
However, for continued approvals, developers are required to conduct confirmatory clinical trials to prove their direct clinical benefit. At the same time, these partially proven drugs may remain on the market, in some cases generating billions of dollars in sales for developers, even if their confirmatory trials are delayed.
The agency’s fast-track approvals peaked in 2020 with 47 such approvals before dropping to 25 and 15 in 2021 and 2022, respectively, as the program sparked controversy when the FDA used it to phase out drugs for difficult areas of medicine.
In 2021, the FDA went against the recommendation of its independent experts to authorize Aduhelm, the therapy against Alzheimer’s disease developed by Biogen (IBIB) and Eisai (OTCPK: ESALF) (OTCPK:ESAY), under the accelerated trajectory.
As a result of this decision, the Office of the Inspector General of the Department of Health and Human Services discovered the burden of drugs allowed under expedited approvals but whose confirmatory trials were delayed by at least six months. According to the HHS-OIG, drugs with accelerated approvals and delayed confirmatory trials cost Medicare and Medicaid $18 billion from 2018 to 2021.
According to Bloomberg analysis, confirmatory studies for 19 drugs with fast-track approval had not yet been completed as of April, meaning the trials were late or past their official deadlines. There were seven other drugs whose developers had submitted clinical data to the FDA and therefore were not classified as those with delayed confirmatory trials.
In this context, the FDA takes a strong stance on expedited approvals when confirmatory clinical studies have remained incomplete or have failed.
This year, two hastily approved drugs, including Swiss-based Covis Pharma’s preterm birth drug Makena, were pulled from the market. After a long regulatory battle, Covis, backed by Apollo Global Management (APO), pulled Makena from the market in March after more than a decade since its accelerated approval.
According to Bloomberg Analysisthe loss of fast-track approvals peaked in 2021 and 2022, with seven such drugs released each year.
The fast track has also helped pharmaceutical majors such as Merck (New York stock market :M.K.R.), Bristol Myers Squibb (New York stock market :BMY), AbbVie (New York stock market :ABBV) and Johnson & Johnson (JNJ) to maintain blockbuster status for some of their cancer drugs.
The HHS-OIG findings indicate that Imbruvica, developed by AbbVie (ABBV) and Johnson & Johnson (JNJ), resulted in $707 million spent on Medicare and Medicaid between 2018 and 2021, though some confirmatory trials for the blood cancer drug remained delayed. Meanwhile, Bristo Myers’ Opdivo anti-PD-1 immunotherapy (BMY) cost Medicare and Medicaid $631 million during the period.
Some drugmakers’ business models rely entirely on expedited approvals. Therapeutic Sarepta (NASDAQ:SRPT) has obtained accelerated approval from the FDA for the three drugs in its portfolio, generating $2.5 billion in sales over the years to 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 other two drugs. Exondys 51 cost Medicare and Medicaid $674 million in 2018-21 because its confirmatory trial did not start even four years after approval.
Since then, the FDA has strengthened its accelerated approval program. In December, Congress passed legislation that, among other things things, required developers to have confirmatory clinical trials underway at the time of approval.
Zarephath (SRPT) attributes its delays for the Exondys 51 program to various factors, including certain requirements imposed by the FDA. The company aims to complete a confirmatory study for Exondys in 2024 and for its other two drugs a year later.
Meanwhile, thanks to accelerated approvals, Sarepta (SRPT) is also expanding its gene therapy program which, according to Chief Executive Douglas Ingram, “would not have existed without Exondys’ approval.”
By May 29, the biotech is on course to win the green light from the FDA for its Roche (OTCQX: RHHBY) (OTCQX: RHHBF) in partnership with Duchenne SRP-9001 gene therapy after an FDA advisory board backed its acceleration approval about a week ago.