The Accelerated Approval Risk: When Speed Costs You the Asset

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FDA's accelerated approval pathway lets a drug or biologic for a serious condition reach patients on the basis of a surrogate endpoint reasonably likely to predict clinical benefit. The price is a confirmatory trial that has to verify that benefit. For an investor, the question is not only whether the pathway is available but whether the company can carry the confirmatory obligation to its end.

Recent cases show how that obligation plays out: FDA's withdrawal of Makena in 2023, Biogen's 2024 decision to discontinue Aduhelm rather than complete its confirmatory study, and Sarepta's 2025 confirmatory results for two Duchenne therapies.

How Accelerated Approval Works

Section 506(c) of the Federal Food, Drug, and Cosmetic Act, implemented in FDA's regulations at 21 CFR part 314 subpart H for drugs and part 601 subpart E for biologics, allows approval based on a surrogate or intermediate clinical endpoint reasonably likely to predict clinical benefit. The sponsor must then conduct studies to verify that benefit, and if they don't verify it, FDA can withdraw the approval. The pathway defers verification; it doesn't remove it.

What FDORA Changed

The Food and Drug Omnibus Reform Act of 2022 (FDORA), enacted in December 2022 as part of the Consolidated Appropriations Act, 2023, tightened the confirmatory obligation. FDA may now require confirmatory studies to be underway before approval or within a set time after it; sponsors must report on their progress about every 180 days; and FDA has expedited procedures to withdraw an approval, for example when a sponsor doesn't conduct a required study with due diligence. FDA issued draft guidance on accelerated approval in December 2024 and on when a confirmatory trial counts as underway in January 2025.

Confirmatory Delays Are Documented

HHS's Office of Inspector General reported in 2022 that, as of May 5, 2022, 37 confirmatory trials for 35 accelerated approval applications had missed their original planned completion dates, by about 20 months on average, and 14 were more than a year late. OIG also found that from the pathway's start in 1992 through May 2022, 35 of 278 accelerated approval drug applications (13%) had been withdrawn. While a confirmatory trial runs, the sponsor is funding it alongside commercialization, and competitors may pursue traditional approval on fuller evidence.

Recent Cases

• Makena (hydroxyprogesterone caproate): the confirmatory PROLONG trial didn't show a reduction in preterm birth. An FDA advisory committee voted for withdrawal in October 2019, FDA's drug center proposed withdrawal in October 2020, and FDA's final decision to withdraw approval came on April 6, 2023.
• Aduhelm (aducanumab): granted accelerated approval in June 2021. On January 31, 2024, Biogen announced it would discontinue Aduhelm and terminate the ENVISION confirmatory study, citing the time and investment the study would require rather than safety or efficacy.
• Amondys 45 and Vyondys 53 (Sarepta Therapeutics): the ESSENCE confirmatory study didn't meet its primary endpoint, as Sarepta reported in November 2025. Sarepta then sought conversion to traditional approval; FDA accepted its supplemental applications in June 2026, with a target action date of February 28, 2027.

Diligence Red Flags

Signals worth checking in an accelerated approval asset:

• The surrogate endpoint's link to clinical outcome is weak or contested
• The confirmatory trial is enrolling slowly against plan, or has slipped past its planned completion
• The company's runway ends before the confirmatory readout
• The confirmatory trial's comparator may be overtaken as the standard of care changes
• FDA required the trial to be underway at approval, and it isn't on track

When Accelerated Approval Fits

For serious conditions with high unmet need, accelerated approval can bring a therapy to patients years earlier. How well it works depends on how strongly the surrogate predicts the outcome that matters, and that varies by disease and endpoint. Matching the pathway to the biology matters more than matching it to timeline pressure.

After Approval

A credible accelerated approval plan treats the confirmatory trial as a top post-approval priority, with dedicated trial operations, the progress reporting FDORA requires, and a plan for what happens if the primary endpoint underperforms. For investors, the diligence question is whether the company has the operational and financial footing to finish the confirmatory trial.