The accelerated approval pathway is evolving in plain sight, with or without congressional help – Endpoints News

FDA leaders have made it clear that reforming the accelerated approval pathway is a priority, and with several recent actions, the agency has signaled that it is willing to take action on those reforms even without immediate movement from Congress.

The latest sign of this evolution occurred today, as GSK announced it was pulling its fifth-line multiple myeloma drug Blenrep at the FDA’s request — just 15 days post-confirmatory trial fail announcement.

The urgency in the FDA’s request shows the extent to which the agency is becoming more nimble. In other AA cases, such as with the failed confirmatory trial for Covis’ preterm birth drug Makena in 2018, the agency’s ability to pull the drug has been delayed by four years, with a recent hearing that should lead to a final decision in the coming months.

Reshma Ramachandran, assistant professor in the Department of Medicine at Yale University, told Endpoints News that the Blenrep move is “definitely a sign that FDA is taking steps to transform the AA [ac­cel­er­at­ed ap­proval] without Congress explicitly giving them authority. Technically, Congress does not need to, given how broad the statute is currently, but it does prevent FDA from either making such changes as exceptions or being called out by companies for veering away from regulatory precedent.”

But without congressional action, there may be gaps between how quickly some of the larger pharma companies pull their AAs and aren’t as financially impacted by those pulls, compared with smaller companies that may only have one or a few accelerated approvals in their pipelines.

Rachel Sachs, law professor at Washington University School of Law in St. Louis, noted to Endpoints that the statute specifies that expedited withdrawal proceedings must include an opportunity for an informal hearing, so if a company insists on a hearing, “it’s not clear to me FDA can decline. (The company does not have to insist on one, of course.)”

Other AA reforms left out of the user fee package sought to ensure a more timely withdrawal process for accelerated approvals, as well as to provide the agency with the authority to require confirmatory trials to be up and running prior to granting an accelerated approval.

Officials from the FDA’s Oncology Center of Excellence made clear in a recent paper the need to ensure these confirmatory trials are underway when an AA is granted, as they showed the median time to withdrawal is 3.8 years if the confirmatory trial was ongoing at the time of approval, compared with 7.3 years if such a trial had not been initiated.

And the FDA has taken care of the data and reform requests. ADC Therapeutics earlier this month announced that it had to delay a submission because the FDA requested that a confirmatory trial be fully enrolled prior to the filing, with the company noting that FDA

provided strong guidance that, for it to consider an accelerated approval path, a randomized confirmatory Phase 3 study must be well underway and ideally fully enrolled at the time of any BLA filing.

The agency last month even turned over a new leaf when it came to transparency in explaining why it wouldn’t pull an AA for Jazz Pharmaceuticals’ second-line treatment for adults with metastatic small cell lung cancer despite a failed confirmatory trial.

So what was the catalyst for all of this recent action and reform talk? Most likely the FDA’s much-criticized decision to unexpectedly grant an accelerated approval for Biogen’s controversial Alzheimer’s drug Aduhelm, which ended up flopping commercially when CMS requested more trials.

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