New Law Could Make Accelerated Approval Stricter, If FDA Enforces It

The FDA’s accelerated approval pathway will see major changes following December’s passage of the Consolidated Appropriations Act, 2023 (2023 CAA), the latest version of the annual legislation that funds the federal government. Experts say that the changes should force drugmakers to be more diligent about proving the clinical value of their early-stage pharmaceuticals — as long as the FDA uses its enforcement powers.

Stakeholders across the health care system have criticized the FDA’s approach to accelerated approval in recent years. The agency’s critics say that it has taken a lax approach, granting accelerated approval to drugs of dubious clinical value, which ultimately costs the health care system billions. In particular, the FDA’s move to grant accelerated approval to Biogen Inc.’s Alzheimer’s drug Aduhelm (aducanumab) faced criticism from researchers, medical practitioners, health systems and insurers. In addition, a recent congressional report documented ethical lapses by agency employees during the accelerated approval process for Aduhelm, and the HHS Office of Inspector General is currently investigating the agency’s decision.

The accelerated approval pathway, which the agency launched in the 1990s after a direct-action campaign by HIV/AIDS activists, is meant to provide patients with uncurable, terminal illnesses access to early-stage, unproven treatments. Instead of meeting the standard for traditional approval, accelerated approval drugs must only show evidence that they are making progress toward meeting “surrogate endpoints that are ‘reasonably likely’ to predict clinical benefits, rather than those clinical benefits themselves,” according to Rachel Sachs, a pharmaceutical policy expert, attorney and professor at the Washington University School of Law. But drug sponsors often don’t advance confirmatory trials.

Accelerated Approval Withdrawals Are Rare

Drug sponsors are supposed to conduct ongoing trials in order to eventually meet the traditional drug approval standard at a later date, and they’re required to withdraw drugs if they don’t show progress. In practice, that rarely happens. And the FDA has infrequently made an effort to remove accelerated approval drugs that ultimately don’t show clinical value from the market. According to an NPR investigation, the FDA has withdrawn 28 accelerated approvals out of hundreds that have been granted, and each withdrawal took an average of seven years to complete.

That fraught process has come under scrutiny in recent months, as the FDA moved to withdraw Covis Pharmaceuticals Inc.’s Makena (hydroxyprogesterone caproate), a drug meant to reduce the incidence of preterm birth for at-risk pregnant people. The drug was granted accelerated approval in 2011, but recent trials have not demonstrated that earned it earned the designation. The FDA recommended withdrawing Makena in the fall.

“Since then, the FDA has said that it has failed to prove clinical benefit, so they sought to withdraw it,” said Lauren Bloch, director of health policy and regulatory affairs at Faegre Drinker LLP, during a Jan. 10 webinar on the 2023 CAA. “That’s something that they have the authority to do, but there was a good deal of controversy around whether there was really a failure to prove clinical benefit, and whether it should have been kept off the market.”

FDA Gains More Authority to Withdraw Accelerated Approval Drugs

That dispute over the FDA’s authority, Bloch said, is one reason for the 2023 CAA’s accelerated approval reforms.

“Especially in recent years, there have been questions about whether the FDA had clear authority to take [withdrawal] actions related to accelerated approval,” Bloch added. “The general thought was that they did, but that these [powers] were vague. So when FDA Commissioner [Robert] Califf took office, he actually had advocated for the FDA receiving strengthened authority on this topic. At least in concept, these provisions were something that the FDA supported, and not something that Congress did out of the blue.”

The 2023 CAA is meant to step up the FDA’s ability to track accelerated approval drugs and withdraw unproven drugs from the market, according to a Jan. 10 post by Joanne Hawana, an attorney at Mintz Levin PC:

  • The FDA can now require a drug sponsor to have a confirmatory trial underway before approval is awarded.
  • Drug sponsors must submit progress reports on post-approval studies every six months, until the study is completed.
  • The FDA now has “the option of using expedited procedures to withdraw approval after the confirmatory trial fails to verify the product’s clinical benefit.”
  • The agency is required to explain on its website why it does not require a post-approval study if it allows a sponsor to gain accelerated approval without one.
  • The law creates an Accelerated Approval Council with members from other federal agencies to “ensure the consistent and appropriate use” of accelerated approval. The council will meet three times per year and publish an annual report.

However, Hawana also noted that the new law “does not include previous congressional proposals to require specific labeling information regarding the nature of a drug’s accelerated approval and disclosing that studies are ongoing to verify clinical benefit.”

“The agency now has much more clear authority to require sponsors to provide details on things like trial design, enrollment, goals, and milestones prior to that drug ever receiving approval,” Bloch said during the Faegre Drinker webinar. “Although this was really commonly done for cancer clinical trials, a criticism of accelerated approval is that the FDA was not very good about enforcing sponsors’ completion or even initiation of these trials. Sometimes these trials would take years to start and then would drag on for many years. And that’s really not how accelerated approval was intended [to work]. So this will allow the FDA [to] be much more firm, and make sure that sponsors really are planning to do those trials — and have a clear plan to do so even before they receive approval for their product.”

FDA’s Actions Will Determine Law’s Success

“I do think it’s a step in the right direction, in terms of getting the FDA further oversight, to make sure there’s not unnecessary delays” in trials and withdrawals, Reshma Ramachandran, M.D., assistant professor of medicine at Yale University, tells AIS Health, a division of MMIT. The reforms will also allow for “more public knowledge and transparency about the progress of these confirmatory trials.”

The reforms do “at least put the ball in FDA’s court in terms of having a more standardized process for withdrawing the drug,” Ramachandran says, “instead of what we’re seeing now with Makena, where FDA is consistently recommending withdrawal of the drug, but the sponsor has decided not to go forward with voluntary withdrawal,” leading to an arbitration process that is “taking forever.”

But Ramachandran says that giving the FDA more authority won’t solve all of accelerated approval’s problems. The agency has to want to use that authority.

“A lot of it will depend on implementation, because there’s still room for flexibility for the sponsors,” Ramachandran tells AIS Health. Sponsors can “request that FDA give them further discretion around completion of confirmatory trials and what is going to lead to withdrawal.”

Also, Ramachandran says, it’s not clear what will happen to drugs that have already been granted accelerated approval.

“I would hope for a number of standing accelerated approval drugs, where they’ve yet to convert to a traditional approval or be withdrawn from the market, that those progress reports would be made available,” Ramachandran says. “But the legislation itself doesn’t clearly indicate if it’s going to be starting from the implementation of the legislation and the approvals thereafter, or if it can be retroactive. It kind of leaves the door open.”

Contact Ramachandran at

This article was reprinted from AIS Health’s biweekly publication RADAR on Drug Benefits.

© 2024 MMIT
Peter Johnson

Peter Johnson

Peter has worked as a journalist since 2011 and has covered health care since 2020. At AIS Health, Peter covers trends in finance, business and policy that affect the health insurance and pharma sectors. For Health Plan Weekly, he covers all aspects of the U.S. health insurance sector, including employer-sponsored insurance, Medicaid managed care, Medicare Advantage and the Affordable Care Act individual marketplaces. In Radar on Drug Benefits, Peter covers the operations of (and conflicts between) pharmacy benefit managers and pharmaceutical manufacturers, with a particular focus on pricing dynamics and market access. Before joining AIS Health, Peter covered transportation, public safety and local government for various outlets in Seattle, his hometown and current place of residence. He graduated with a B.A. from Colby College.

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