Accelerated Approval

An FDA instituted program that allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need.

What is accelerated approval?

An FDA instituted program that allows for earlier approval of drugs that treat serious or life-threatening conditions and fill an unmet medical. Accelerated approvals rely on the measurement of surrogate endpoints as a measure of clinical benefit to the patients. Drugs that meet the standard for traditional approval are not eligible for accelerated approval.

When is accelerated approval used?

Accelerated approval is used when a disease course is long and measuring the clinical benefit would require significant time. Examples are drugs used to treat certain cancers or HIV infection where an effect on tumor growth or viral load can be demonstrated quickly but the effect on survival is long-term because of the typical disease course.

Another scenario in which accelerated approval is used are acute diseases where a large study would be needed to show clinical benefit because of the rarity of the event but a surrogate endpoint is available that can be used in a much smaller and therefore faster study.

What are the risks associated with accelerated approval?

The main risks associated with accelerated approval are:

  • Surrogate endpoints are used because they are assumed to predict clinical benefit. Should that not be the case, patients are exposed to drugs that ultimately do not provide a clinical benefit.
  • Shorter, fewer and smaller clinical trials result in less information about rare or delayed adverse events.

Which drugs qualify for accelerate approval?

These risks are the reason why accelerated approval is limited to drugs that demonstrate an effect on an endpoint that is reasonably likely to predict clinical benefit and that fulfill the following requirements:

  • Treat serious conditions
  • Provide a meaningful therapeutic benefit over existing treatments

What are the conditions for obtaining accelerated approval?

Drugs granted accelerated approval need to meet the same effectiveness and safety standards as drugs undergoing traditional approval. Basis for approval by the FDA is that the surrogate endpoint is “reasonably likely to predict the intended clinical benefit”. This decision is a judgement call based on biological plausibility and clinical data showing that relationship. Any concerns about the relationship between the surrogate endpoint and clinical benefit get resolved in post-approval studies.

In addition, the company applying for accelerated approval must meet the following conditions:

  1. Submit copies of all promotional materials to be used
  2. Conduct post-marketing, confirmatory trials to verify the anticipated clinical effect.

A company planning on seeking accelerated approval should start discussions with the review division of the FDA during development and provide data supporting the use of the chosen surrogate endpoint as well as the planned confirmatory trials.

Can accelerated approval be withdrawn?

Yes, the FDA can withdraw accelerated approval for the following reasons:

  • Clinical benefit cannot be shown in a trial
  • The drug is shown to be not effective or safe based on other evidence
  • Post-approval trials are not conducted with the necessary degree of due diligence by the applicant
  • The applying company disseminates false or misleading information about the product.

The European equivalent of the US accelerated approval is the conditional marketing authorisation granted by the European Medicines Agency.


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