The FDA Accelerated Approval Designation: A Primer

Picture1By Peter Martin, M.D.

As a response to the HIV/AIDS crisis of the 1980s the United States FDA developed guidelines for the Accelerated Approval designation in 1992. The purpose was to speed up the approval process and provide new treatments to the patients most in need. The program was an instant improvement, resulting in the approval of 80 drugs, including 29 cancer drugs, in the first decade, and was subsequently updated as part of the Food and Drug Administration Safety and Innovation Act in 2012. Under these guidelines the FDA can designate the Accelerated Approval label for new treatments that address a serious medical condition, and which are thought to offer a meaningful advantage over existing therapies.

The FDA’s criteria for making this designation is based on the scientific support for the measurement of surrogate or intermediate clinical endpoint in the treatment, and the likelihood it will predict a clinical benefit compared to available therapies in an area of unmet need. For example, in the past it may have been necessary for a new drug to prove a survival advantage compared to standard therapy in the context of a randomized phase III trial. It could take up to a decade to reach this benchmark for approval. Under the Accelerated Approval designation, a drug might be approved for an unmet need if it could demonstrate tumor shrinkage based on radiological imaging, which would likely be associated with a durable clinical benefit. Because the FDA requires a high degree of scientific support for the use of a surrogate endpoint, drugs that are approved under the Accelerated Approval program usually go on to receive full approval 3-4 years later on average, following the completion of confirmatory studies demonstrating clinical benefit.

This is not always the case, however, and some drugs that receive Accelerated Approval designation are subsequently withdrawn from the market when a confirmatory study fails to provide sufficient evidence of clinical benefit (e.g., bevacizumab for breast cancer). There is also the risk that a drug that had received accelerated approval will later demonstrate significant side effects during larger studies (e.g., this was part of the reason that gemtuzumab ozogamicin was withdrawn from the market in 2010). Other times, an application for accelerated approval might be denied, but the drug eventually receives full approval following completion of larger studies (e.g., TDM-1 for breast cancer). The definition of “unmet need” is another stumbling block to efficient drug development. Some developers might perceive an unmet need in settings where all available therapies have been exhausted, while the true need lies much earlier in the course of a disease where available therapies provide only limited benefit.

The Accelerated Approval program has provided access to dozens of drugs years earlier than they would otherwise have become available, improving the lives of countless patients with cancer and other conditions. However, the designation is not a panacea.  Physicians and patients should be aware of the evidence behind the designation of a given drug and should continue to follow the drug development process as new information comes to light.

Previous Entries in the Primer Series

The FDA Approval Process
The FDA Breakthrough Therapy Designation

Author: lymphomaprogram

Located on the Upper East Side of New York City, the Lymphoma Program at Weill Cornell Medical College/NewYork Presbyterian Hospital is internationally recognized for our efforts to enable patients with non-Hodgkin lymphoma, Hodgkin disease and related disorders to have the best possible clinical outcome, including cure when possible.

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