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RMAT vs. Breakthrough vs. Fast Track: Companies Seek Clarity on FDA Draft Guidance

Posted 19 February 2018 | By Zachary Brennan 

RMAT vs. Breakthrough vs. Fast Track: Companies Seek Clarity on FDA Draft Guidance

Industry groups BIO, Biocom, the Alliance for Regenerative Medicine and the International Society for Cellular Therapy (ISCT), as well as biopharma company Gilead, are seeking clarity from the US Food and Drug Administration (FDA) on guidance related to its relatively new Regenerative Medicine Advanced Therapy (RMAT) designation, according to comments submitted last week.


The 21st Century Cures Act created the RMAT designation to speed the review of cell therapies, therapeutic tissue engineering products, human cell and tissue products or any combination product using such therapies or products if it “is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition” and “preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.”

Hailed as a way to speed such regenerative treatments to US patients in need, the designation has already been sought by dozens of companies as Peter Marks, director of FDA's Center for Biologics Evaluation and Research (CBER), said in November that the agency had received 34 RMAT designation requests, acted on 31 requests and granted 11 RMAT designations. 

Humacyte and Vericel are two examples of companies that have received the designation for their products.

Advantages of the RMAT designation include all the benefits of the fast track and breakthrough designations, including early interactions between the agency and sponsors, though unlike the breakthrough designation, the RMAT designation does not require evidence to indicate that the drug may offer a substantial improvement over available therapies.


How FDA distinguishes between the level of evidence necessary to obtain an RMAT vs. the breakthrough and fast track designations is one of the areas stakeholders are seeking additional clarity from FDA.

For instance, Biocom noted that the level of evidence required for RMAT designation “appears to fall in-between the standards for breakthrough therapy designation and fast track designation.

“RMAT designation, like breakthrough therapy designation, can be obtained through preliminary clinical data, but it only requires that preliminary clinical evidence shows that the product has the potential to address an unmet medical need, rather than a substantial improvement over existing therapies on one more clinically significant endpoints. We believe that the final guidance should indicate clearly that the level of evidence required for RMAT designation requires less evidence than breakthrough therapy designation but more than fast track designation,” Biocom said.

The Alliance for Regenerative Medicine also said it would be helpful if FDA clarified in the guidance if there are any additional benefits of the breakthrough designation if a sponsor has already received an RMAT designation, or vice versa. The alliance also broke down the similarities in the following chart:

Echoing those comments, industry group BIO called on FDA to provide further guidance on whether the RMAT or breakthrough therapy designation “is more appropriate for different types of programs.” The group also sought “further clarity on how accelerated approval and post approval requirements may be used for RMAT designated products.”

Gilead, meanwhile, is seeking examples from FDA on the type of preliminary clinical evidence that would be suitable to support an RMAT designation. “For example, would data from a similar product be acceptable?” the company asked.

And the ISCT expressed concerns about process improvements and sought additional information from FDA on “manufacturing changes to the commercial process and how it can affect eligibility for the expedited pathways.

This appears to be antithetical to the evolution and development of RMAT if the ability to make process improvement is hobbled.

“The level of change that is considered significant should be delineated. The loss of RMAT designation in this instance is serious. Sponsors would be concerned about the loss of RMAT designation upon every tweak of a process,” ISCT said.

The American Society for Gene and Cell Therapy also recommended the inclusion of gene therapy in the definition of regenerative medicine and that FDA support the resulting eligibility of gene therapies for consideration for RMAT designation.



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