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YOUR GO-TO SOURCE FOR ANALYSIS OF ISSUES AFFECTING THE PHARMA & BIOTECH SECTORS

At the Food and Drug Law Institute’s 2021 annual conference, Dr. Peter Marks, the director of FDA’s Center for Biologics Evaluation and Research, commented on progress that has been made using FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation. As quoted in the Pink Sheet, Dr. Marks stated that the RMAT designation is a “nice tool to have in our tool belt . . . . It may not be an earth-shattering new tool but it’s a nice tool just the same.”

Dr. Marks further indicated that it may be easier for sponsors to obtain an RMAT designation as compared to its older sibling, the breakthrough therapy designation, stating, “As it’s come to evolve, the fact that the standard is a little bit lower to receive this designation . . . allows us to designate products that might not have quite the same amount of clinical information.” Unlike breakthrough therapy designation, which requires that sponsors demonstrate that a product may result in a substantial improvement over available therapies on clinically significant endpoints, the RMAT designation only requires a demonstration of the potential to address an unmet medical need using preliminary clinical evidence. This is especially important for regenerative medicines, which, as noted by Dr. Marks, may be “earlier on and are a little bit harder to study early on in their development.”

Currently, however, the breakthrough therapy and RMAT designation rates appear to be relatively comparable. Specifically, between the end of December 2016 and beginning of January 2017, FDA received 66 requests for breakthrough therapy designation and approved 28, resulting in about a 42% designation rate. During this same period, FDA received 165 RMAT designation requests and approved 63, providing a 38% designation rate. Despite the designation rates, the real testament to the RMAT program will be whether it actually facilitates product approvals. Given that it is only recently that a critical threshold of regenerative medicines entered later-stage trials, in the coming years we should see more sponsors submitting regenerative medicine marketing applications to FDA.

Once more regenerative medicines reach the approval stage, what will also be telling is whether and what kind of postapproval data may be required. As noted by FDA in its RMAT guidance, if “an RMAT receives accelerated approval . . . it may be appropriate for sponsors to provide post-approval clinical evidence about the product through expansion [of existing studies] to additional sites.” Sponsors may also be able to fulfill any postapproval study requirements through data sources “other than the traditional confirmatory clinical trials.” This was specifically noted by Dr. Marks. As quoted in the Pink Sheet, Dr. Marks stated, “One of the things that I actually can start to see the benefits of [is] this concept that as for fulfillment of a postmarketing commitment, we could use larger datasets from an existing clinical trial, in other words just . . . enroll more people on a clinical trial to fulfill a postapproval commitment, or to just have longer follow-up periods as the statute lets us for people enrolled in a trial . . . . Those may turn out to be very useful provisions.”

Given the foregoing, sponsors developing regenerative therapies may want to give thought to the RMAT designation because as more products reach later-stage development, we should begin to see the fruits of FDA’s RMAT labor. Sponsors that previously applied for RMAT designation and received denials due to insufficient clinical evidence may also want to consider whether their later-stage trials support designation as the designation’s advantages extend beyond the preapproval phase and potentially extend to more flexible postapproval study requirements.

Finally, one sector that may not have previously considered the RMAT designation but for which the designation may now be useful is stem cell processing, as the US Court of Appeals for the Eleventh Circuit just issued its opinion in United States v. U.S. Stem Cell Clinic, LLC, et al., finding that procedures in which a patient’s adipose tissue is removed for stem cell isolation and reinjection do not qualify for FDA’s exemption for human cell and tissue products (HCT/Ps). As stem cell processing facilities consider how this opinion relates to their operations and whether they need to obtain FDA approval for their products, they may also want to consider whether the RMAT designation would assist them with product development and eventual approval.