WASHINGTON — Expedited drug approvals slowed this year as the Food and Drug Administration’s controversial accelerated pathway got here underneath new scrutiny from Congress, authorities watchdogs and a number of the company’s personal leaders.
With lower than a month remaining within the year, the FDA’s drug heart has granted 10 accelerated approvals — fewer than the tally in every of the final 5 years, when use of this system reached all-time highs.
The program permits medication to launch within the U.S. based mostly on promising early outcomes, earlier than they’re confirmed to profit sufferers.
Academics have lengthy complained that the observe has resulted in a glut of high-priced, unproven drugs, notably for most cancers. But final year’s accelerated approval of a much-debated Alzheimer’s drug touched off a brand new spherical of criticism, together with investigations of FDA’s resolution making by federal inspectors and Congress.
A current FDA hearing geared toward revoking approval from an unproven preterm birth drug additional underscored this system’s shortcomings. FDA has been attempting to get the drug, Makena, off the market for greater than two years, as a result of a follow-up examine confirmed it did not profit infants or moms. The producer has refused to cooperate.
Amid the newest controversy, FDA leaders have taken unprecedented steps suggesting a harder stance on accelerated approval: nudging drugmakers to take away a rising checklist of unproven makes use of for medication and asking Congress for brand spanking new powers to expedite removals when corporations balk.
Dr. Reshma Ramachandran, a Yale University researcher who helps congressional reforms, believes the current scrutiny of the accelerated approval course of “definitely led to them pausing and taking a different path.” Still, Ramachandran and different critics say it’s too early to inform if FDA’s current actions replicate a longer-term coverage shift.
An FDA spokeswoman stated the company’s posture on accelerated approval “has remained consistent and the agency is committed to ensuring the integrity of the program.” She added that FDA is utilizing “every authority at our disposal” to verify drugmakers rapidly conduct confirmatory research after approval.
Launched in 1992, the accelerated approval program is credited with rushing the supply of early breakthroughs for HIV and most cancers. About 300 drug approvals have been made that approach, almost half of them within the final 5 years.
But researchers and authorities watchdogs have chronicled issues with FDA’s oversight, together with delays in rapidly eradicating medication with failed or lacking confirmatory research. Federal inspectors not too long ago discovered that 40% of accelerated approvals had incomplete affirmation research.
The image is starting to alter. In lower than two years, the FDA has efficiently referred to as on drugmakers to take away greater than 20 approvals from accelerated medication — primarily cancer therapies — that failed to point out a profit. That’s greater than half the withdrawals in this system’s historical past.
FDA’s most cancers chief, Dr. Rick Pazdur, has referred to this effort of clawing again approvals as his “jihad.”
Several drugmakers recently declined FDA requests to voluntarily pull their drugs. That’s raised the specter of more long, onerous public hearings to force removal, a process Pazdur called “a nightmare.”
The ability to require drugmakers to have their studies underway before approval is one part of legislation that congressional lawmakers hope to attach to a massive, end-of-the-year spending bill. If passed, it would be the biggest overhaul in accelerated approval’s 30-year history.
“We need more teeth in terms of getting the confirmatory trials started before accelerated approval,” FDA Commissioner Robert Califf said at a recent cancer conference. “Once approval occurs it’s very difficult to hold back the marketeers.”
FDA regulators are already testing out the approach. Increasingly, the agency is telling drugmakers they must have their confirmation studies underway before approval.
“We know the FDA has raised the bar for accelerated approval, and so that’s why we’re seeking additional clarity on their position,” Mike Sherman, CEO of startup Chimerix, told investors on a recent call discussing the company’s plans for an upcoming cancer drug.
A higher bar could spell trouble for smaller drugmakers, who often rely on accelerated approval to gain a market foothold before raising additional funds.
To be sure, FDA approval trends are impacted by a variety of forces. The agency’s overall tally of novel drugs is down markedly this year at about 30, compared with 50 last year. And even the recent peak in use of the accelerated pathway — 45 approvals in 2020 — reflected several trends.
Drugmakers have been aggressively pursuing a new class of “immunotherapies” that help the body recognize and attack cancer. The FDA has granted more than 80 uses for those drugs since 2015, pushing up annual accelerated approval tallies.
Additionally, COVID-19 pandemic disruptions forced some drugmakers to cut short their research plans, asking FDA for accelerated approval based on partially completed studies, instead of a full results.
“There was a lot of reinterpretation of the FDA rules to make sure those companies could proceed, otherwise they would have lost billions of dollars,” said Sam Kay, a consultant with Clarivate, which advises pharmaceutical companies.
It’s a reminder of how much flexibility the FDA has.
Many of the reforms pending in Congress “are things the FDA could do now,” notes Ramachandran.
“I think having Congress do it gives them the cover and blessing to carry forward with what they want to do,” she said.
Follow Matthew Perrone on Twitter: @AP—FDAwriter
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