It’s imperative that life-saving therapies for serious diseases are readily available, especially if it is the first available treatment. With this in mind, the FDA instituted Accelerated Approval (AA) regulations as an approach to allow drugs for serious conditions to be approved based on a surrogate endpoint.

In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA). Section 901 of FDASIA allows the FDA to grant AA, for drugs that treat serious conditions and fill an unmet medical need, based on whether the drug has an effect on a surrogate or an intermediate clinical endpoint.¹

Studies for drugs can take many years to yield results on clinical benefit, but patients afflicted with serious diseases need treatment as soon as possible. AA using a surrogate endpoint enables the FDA to approve life-saving drugs faster.

A surrogate endpoint is a marker or measure that predicts clinical benefit, but is not a measure of clinical benefit. Similarly, an intermediate clinical endpoint is a measure of a therapeutic effect that is likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality. The FDA accepts proposed surrogates or intermediate clinical endpoints based on the scientific support for that endpoint. Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors. Pharmaceutical companies must conduct studies to confirm clinical endpoints, these are referred to as phase IV confirmatory trials; for the aforementioned example, that would mean determining if the patients actually live longer. Approval of a drug may be withdrawn if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit.¹

Hundreds of drugs have been granted AA since the pathways’ inception. In a 2018 assessment of the AA pathway, only 5% of accelerated drug approvals had been withdrawn or revoked.²

From 1992 to 2017, nearly 70% (64 out of 93) of AA were for malignant hematology and oncology products.³

1. Accelerated Approval. U.S. Food and Drug Administration. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval.

2. Gyawali B, Hey SP, Kesselheim AS. Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval. JAMA Intern Med. 2019;179(7):906-913. doi:10.1001/jamainternmed.2019.0462

3. Beaver JA, Howie LJ, Pelosof L, et al. A 25-Year Experience of US Food and Drug Administration Accelerated Approval of Malignant Hematology and Oncology Drugs and Biologics: A Review. JAMA Oncol. 2018;4(6):849–856. doi:10.1001/jamaoncol.2017.5618