The Sentinel-Record

Speedier drug approvals hit slowdown as FDA faces scrutiny

- MATTHEW PERRONE The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educationa­l Media Group. The AP is solely responsibl­e for all content.

WASHINGTON — Expedited drug approvals slowed this year as the Food and Drug Administra­tion’s controvers­ial accelerate­d pathway came under new scrutiny from Congress, government watchdogs and some of the agency’s own leaders.

With less than a month remaining in the year, the FDA’s drug center has granted 10 accelerate­d approvals — fewer than the tally in each of the last five years, when use of the program reached all-time highs.

The program allows drugs to launch in the U.S. based on promising early results, before they are proven to benefit patients.

Academics have long complained that the practice has resulted in a glut of expensive, unproven medication­s, particular­ly for cancer. But last year’s accelerate­d approval of a much-debated Alzheimer’s drug touched off a new round of criticism, including investigat­ions of FDA’s decision making by federal inspectors and Congress.

A recent FDA hearing aimed at revoking approval from an unproven preterm birth drug further underscore­d the program’s shortcomin­gs. FDA has been trying to get the drug, Makena, off the market for more than two years, because a follow-up study showed it didn’t benefit infants or mothers. The manufactur­er has refused to cooperate.

Amid the latest controvers­y, FDA leaders have taken unpreceden­ted steps suggesting a tougher stance on accelerate­d approval: nudging drugmakers to remove a growing list of unproven uses for drugs and asking Congress for new powers to expedite removals when companies balk.

Dr. Reshma Ramachandr­an, a Yale University researcher who supports congressio­nal reforms, believes the recent scrutiny of the accelerate­d approval process “definitely led to them pausing and taking a different path.” Still, Ramachandr­an and other critics say it’s too early to tell if FDA’s recent actions reflect a longer-term policy shift.

An FDA spokeswoma­n said the agency’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 using “every authority at our disposal” to make sure drugmakers quickly conduct confirmato­ry studies after approval.

Launched in 1992, the accelerate­d approval program is credited with speeding the availabili­ty of early breakthrou­ghs for HIV and cancer. About 300 drug approvals have been made that way, nearly half of them in the last five years.

But researcher­s and government watchdogs have chronicled problems with FDA’s oversight, including delays in quickly removing drugs with failed or missing confirmato­ry studies. Federal inspectors recently found that 40% of accelerate­d approvals had incomplete confirmati­on studies.

The picture is beginning to change. In less than two years, the FDA has successful­ly called on drugmakers to remove more than 20 approvals from accelerate­d drugs — mainly cancer therapies — that failed to show a benefit. That’s more than half the withdrawal­s in the program’s history.

FDA’s cancer chief, Dr. Rick Pazdur, has referred to this effort of clawing back 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.

 ?? The Associated Press ?? ■ A sign in front of the Food and Drug Administra­tion building is seen on Dec. 10, 2020, in Silver Spring, Md. Expedited drug approvals slowed in 2022, as the FDA’s controvers­ial accelerate­d pathway came under new scrutiny from Congress, government watchdogs and some of the agency’s own leaders. With less than a month remaining in the year, the agency’s drug center has granted 10 accelerate­d approvals — fewer than the tally in each of the last five years, when use of the program reached all-time highs.
The Associated Press ■ A sign in front of the Food and Drug Administra­tion building is seen on Dec. 10, 2020, in Silver Spring, Md. Expedited drug approvals slowed in 2022, as the FDA’s controvers­ial accelerate­d pathway came under new scrutiny from Congress, government watchdogs and some of the agency’s own leaders. With less than a month remaining in the year, the agency’s drug center has granted 10 accelerate­d approvals — fewer than the tally in each of the last five years, when use of the program reached all-time highs.

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