Expert Weighs In On New FDA AA Guidance for Cancer

Ravi B. Parikh_courtesy self

Pictured: Ravi Parikh, M.D./Self courtesy

Updated: April 4, 2023

Ravi B. Parikh, M.D., joined BioSpace for a question and answer session on accelerated approval (AA) for cancer drugs. He discussed the process and how the FDA handles AA with these treatments. 

The newly released FDA guidance will significantly affect AA for cancer drugs in the following ways:

  1. "Decreasing reliance on surrogate endpoints for initial FDA AA and encouraging approval based on clinical endpoints
  2. Ensuring that confirmatory Phase III trials are conducted more quickly when a 'two-trial' approach is required
  3. Encouraging a 'one-trial' approach where randomized trials that are powered for downstream clinical endpoints are initially performed, and accelerated approval may be granted on an intermediate endpoint."

The interview has been edited for clarity and length. 

Q: What is the AA designation from the FDA, and how does it differ from traditional drug approval? 

A: Drug indications are granted AA based on surrogate endpoints, usually based on nonrandomized studies, and are subsequently required to confirm clinical benefit. That differs from traditional drug approval, typically based on hard clinical endpoints and usually on randomized studies.

Q: What types of cancer drugs are eligible for accelerated approval, and what criteria must they meet? 

A: Any cancer drug is eligible for accelerated approval. To be granted accelerated approval, a drug must treat a serious condition like cancer and demonstrate a positive impact on a surrogate endpoint likely to indicate clinical benefit (such as overall survival). Drugs granted accelerated approval are required to conduct confirmatory Phase III testing.

Q: How are clinical trials designed and conducted to support accelerated approval of cancer drugs? 

A: Usually, trials are designed with a surrogate endpoint (e.g., response rate) rather than a clinical endpoint. Additionally, most trials designed to support accelerated approval are single-arm trials and are not compared to an existing standard of care.

Q: What are the potential benefits and risks of accelerated approval for cancer drugs? 

A: The most significant benefit is ensuring speedier drug access for patients, anywhere up to two to five years before they would have had traditional access. That is a good thing. 

However, the risks are that the drug will appear promising for about a quarter of all indications granted AA but will fail the Phase III test. Thus, continued use poses long-term risks without significant evidence of benefit.

Q: What measures are in place to ensure that drugs approved through AA remain safe and effective in the long term? 

A: All AA drugs are supposed to undergo confirmatory trial testing so that their safety and efficacy are larger, and comparative trials can be assessed. Additionally, if efficacy or safety results are not promising from post-AA studies, then the FDA or investigators can aggregate data that supports an indication withdrawal or removal.

Q: What is the role of patient advocacy groups and the FDA in the accelerated approval process for cancer drugs? 

A: Patient advocacy groups can contact and speak with their representatives or FDA officials to voice concerns about or lend support to certain drugs.

Q: How are drug manufacturers incentivized to continue studying and improving drugs approved through accelerated approval? 

A: Sadly, without a post-market commitment or post-market surveillance notice, manufacturers are not often willing to run confirmatory safety trials that are not incentivized appropriately.

Q: How does accelerated approval impact the pricing and accessibility of cancer drugs? 

A: Theoretically, it does not.

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