FDA and industry support fixes to accelerated approval program

Corrected 19 May 2023*

New reforms to the US Food and Drug Administration (FDA) accelerated approval program will give the agency more authority in requiring sponsors to conduct confirmatory studies at the time of drug approval and will shed greater transparency on the status of these studies, according to a panel comprising a high-ranking agency official and industry at the Food and Drug Law Institute (FDLI) Annual Conference on Wednesday.

“The FDORA (the Food and Drug Omnibus Reform Act) legislation gave us new and exciting tools to further improve this program,” asserted Jacqueline Corrigan-Curay, principal deputy center director for FDA Center for Drug Evaluation and Research (CDER).

She said the new law makes it clear that the agency has the authority to require that companies start confirmatory studies before the drug’s approval. “We’ve always had in our regulations that [confirmatory studies] should be underway, but we couldn’t say it must and when someone met all the criteria for accelerated approvals, but the study wasn’t done, we couldn’t say no” and deny approval.
 
FDORA also provides for greater transparency by requiring the FDA to post the status of confirmatory studies every six months instead of every year.  

In addition, the new law calls for all FDA centers that use an accelerated approval pathway to post the status of ongoing studies and list which studies were verified or withdrawn.

The law also creates a more streamlined process for withdrawing drugs when postmarket studies fail to confirm effectiveness. The current process for withdrawing a drug is “quite prolonged and legalistic. The new process is more transparent and allows applicants to appeal these decisions within expedited timelines.”
 
Lastly, it calls for the creation of a new accelerated approval council comprised of members of various agency centers that use accelerated approval to ensure that senior leadership is aligned on accelerated approval policy, said Corrigan-Curay.

“Overall, we are very excited, and I would agree that the accelerated program is working but there is room for improvement, and we’re happy to have these authorities to work from,”she added.  

The accelerated approval program came under criticism last year from the US Department of Health and Human Services Office of Inspector General (OIG), which found that more than one-third of accelerated approval applications do not meet their original confirmatory trial dates, and four drug applications were more than 5 years past their confirmatory trial deadlines (RELATED:  OIG raises concerns about accelerated approval pathway, Regulatory Focus, 30 September 2022).
 
Lilly supports accelerated reforms
 
Maureen Japha, director for health policy and strategy for EIi Lilly, said the company supports the reforms. “The accelerated approval pathway is something that Lilly has been thinking about for some time, and we want to ensure that we can protect this pathway.” She added that it can be challenging to get these studies done but as a general rule “we will initiate these studies prior to accelerated approval.”
 
Last November, the company issued a slate of principles on accelerated approval, stating that  the company is committed to producing confirmatory trial data, and if confirmatory studies fail to verify the drug’s benefit, the company will initiate the decision to withdraw with FDA.
 
“We were really pleased to see that the FDORA provisions were in concurrence with what we laid out here and we feel good about where Congress has confirmed their support of this pathway.”
 
'Fairly significant assault' on accelerated approval
 
John Murphy of the Biotechnology Innovation Organization (BIO) told the group that before FDORA’s enactment, there was a “fairly significant assault” on FDA’s accelerated approval program from the media, the Centers for Medicare and Medicaid Services (CMS), and state governments.
 
He said that “largely speaking after we got through this very negative noise last year in the debate on the FDORA changes, we are very much aligned with the FDA in the accelerated approval space. We would like to see the process as robustly enforced as possible.”
 
One attorney said that before FDORA, FDA was already doing a fairly good job getting companies to withdraw their applications when confirmatory evidence was not forthcoming.

“In the past few years, FDA has been very good and very effective at persuading sponsors to voluntarily withdraw accelerated approvals in situations where the confirmatory trials have not been conducted,” said Michael Stern of Covington and Burling. Stern said that since 2020, 17 oncology accelerated approvals have been voluntarily withdrawn.

FDLI Annual Conference
 

*A previous version of this story misquoted an FDA official on the timing of confirmatory studies. Regulatory Focus regrets the error.