If you didn’t read through all 1,653 pages of the federal omnibus spending bill passed in December 2022, we don’t blame you (we didn’t either and can only imagine it was riveting). But lawmakers snuck into the massive bill several changes to the FDA’s accelerated approval pathway, including new reporting requirements and withdrawal procedures.
Under the pathway, drugmakers aren’t required to prove their drug is clinically beneficial (just that it’s likely to be). After the drug is approved and on the market, the drugmaker must do another trial, called a confirmatory trial, to confirm that the drug is actually beneficial to patients.
The pathway has come under scrutiny in recent years, particularly following the controversial accelerated approval of Biogen’s Alzheimer’s drug called Aduhelm in June 2021.
Industry watchdogs are concerned about the lack of FDA enforcement on the post-approval confirmatory trial.
Historically, the FDA has been quite lax about making sure the trials happen. An NPR investigation found that as of July 2022, 42% of outstanding confirmatory studies either hadn’t started yet or had begun more than a year after approval.
The spending bill grants the FDA more authority to enforce post-approval trial standards. But it remains to be seen how exactly the new law will affect the accelerated approvals pathway.
The changes—most of which originally appeared in the Food and Drug Omnibus Reform Act of 2022 (FDORA)—specifically require that drugmakers submit progress reports every six months on post-approval studies; the Health and Human Services (HHS) secretary specify conditions for post-approval studies no later than the date of accelerated approval; and the HHS secretary establish an accelerated approval council “to ensure the consistent and appropriate use of accelerated approval” across the agency. The wide-ranging legislation also sets procedures the FDA must take before it can withdraw a drug’s accelerated approval status.
FDA spokesperson Jeremy Kahn said the FDORA provisions “will help provide greater assurance at the time of a drug product’s accelerated approval that the confirmatory study will progress in a timely manner and reap high-quality, interpretable results.”
He noted that the agency is “implementing these new authorities by working to streamline processes and determine best next steps.”
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The response from the drug industry is mixed.
Lucy Vereshchagina, SVP of science and regulatory advocacy at the PhRMA, the drug industry’s biggest trade group, told Healthcare Brew that the industry feels issues have been addressed “and there’s no need to make any further changes to the program.”But Pfizer spokesperson Sharon Castillo said there’s still some concern around efforts from the Centers for Medicare and Medicaid Services (CMS) to change reimbursement models for drugs that go through the accelerated approval pathway.
The reforms to the program aren’t going to make a huge difference in how drugmakers operate, but they will have to “make sure that their internal policies and procedures are in compliance with the new legal requirements,” Vereshchagina said.
Castillo said the changes codify many existing practices while preserving regulatory flexibility, and the drugmaker will “continue to leverage the full array of regulatory pathways available, including accelerated approval, depending on patient need, disease severity, and scientific justification,” as well as “adhere to [its] regulatory commitments for timely completion of post-market clinical trials.”
CMS proposed a new payment model in February to incentivize drugmakers to speed up confirmatory trials. Under the model, CMS would reimburse accelerated approval drugs less while confirmatory trials are still underway, and more once the drug’s clinical benefit is confirmed through the trial.
PhRMA also expressed concern over the proposed payment model in a statement with Healthcare Brew saying it is “concerned the proposed accelerating clinical evidence model could compromise patient access to medicines that provide hope for patients without other treatment options, which is exactly the opposite of what the accelerated approval pathway is designed to do.”
Takeda Pharmaceuticals, whose oncology drug Exkivity received accelerated approval in 2021, is reviewing the changes.
“As with any change in regulatory expectations, Takeda thoroughly assesses how these changes to accelerated approval may impact our clinical trials,” Megan Ostrower, a Takeda spokesperson, said in a statement. “Takeda encourages the expanded and responsible use of the program to areas where trial design is particularly difficult, including pediatrics and rare diseases.”
Representatives from Novartis and AstraZeneca declined to comment.