FDA, Guidelines

FDA outlines a laundry list of surrogate endpoints with an eye to expanding the roster for drug developers

The FDA on Wednesday published a list of surrogate endpoints to help inform drug developer discussions with relevant Center for Biologics Evaluation and Research (CBER) or Center for Drug Evaluation and Research (CDER) review divisions.

The list, which was created thanks to the 21st Century Cures Act, includes surrogate endpoints that sponsors have used as primary efficacy clinical trial endpoints for approval of new drug applications (NDAs) or biologics license applications (BLAs). It also includes surrogate endpoints that may be appropriate for use as primary efficacy clinical trial endpoints for drug or biologic approvals, although they have not yet been used to support an approved NDA or BLA.

The list, which will be updated every six months, features surrogate endpoints for numerous diseases including acromegaly, different cancers, chronic kidney disease, cystic fibrosis, hepatitis A, B and C, HIV, hypertension and osteoporosis, among others.

“The acceptability of these surrogate endpoints for use in a particular drug or biologic development program will be determined on a case-by-case basis,” the FDA said.

The list, which separates adult and pediatric endpoints, does not include composite endpoints that are a combination of biomarker surrogate endpoints and clinical endpoints. The table also does not include surrogate endpoints that may have been accepted for past drug development programs but are no longer acceptable as an endpoint to support registration.

And critics of the list note a lack of specificity.

Vinay Prasad

Vinay Prasad, associate professor of medicine at Oregon Health and Science University, told Focus: “I would say, at least for cancer, it is done at such a high level with so little detail, it is pretty much useless. A better summary of surrogates used to justify approvals and their strength can be found in our paper from the Mayo clinic proceedings…We are showing the surrogate used by approval, the pathway of approval, and the strength of the surrogate in the biomedical literature. They just say what surrogates are used in what tumors, but do not explain the line of therapy, the drugs that utilized the pathway or the strength of correlation.”


According to section 507(e)(9) of the Food Drug & Cosmetic Act, “[t]he term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and (A) is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or (B) is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product in accordance with section 506(c).”

First published here. Regulatory Focus is the flagship online publication of the Regulatory Affairs Professionals Society (RAPS), the largest global organization of and for those involved with the regulation of healthcare and related products, including medical devices, pharmaceuticals, biologics and nutritional products. Email news@raps.org for more information. 

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Recursion Pharmaceuticals Salt Lake City, UT
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