FDA Expedited Program Designations to Support Rare Disease Drug Development

More than half of the 1 in 10 Americans affected by rare diseases are children, and the preponderant majority (95%) of the over 7,000 rare diseases do not have an available therapy.¹

For diseases or conditions affecting less than 200,000 individuals in the United States, the FDA Office of Orphan Products Development, OOPD, provides eligible sponsors with two designation programs to facilitate the prevention, diagnosis, and treatment of rare diseases: orphan drug and rare pediatric disease designations.²

Additionally, four principal expedited program and approval pathways are provided by the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER) to expedite development of therapies for serious and life threatening conditions and to address unmet medical need: priority review voucher, fast track designation, breakthrough therapy designation, and accelerated approval.³

Most rare diseases or conditions have a high unmet medical need and are serious or life threatening;⁴ therefore, most qualify for at least one of the four noted expedited programs or designations. In this blog, we discuss the key features of the four expedited programs: rare pediatric disease priority review voucher, fast track designation, breakthrough therapy designation, and accelerated approval.

Rare Pediatric Disease Priority Review Voucher

If a sponsor’s drug, developed as a therapy for a rare pediatric disease, is approved, then that sponsor is awarded a priority review voucher. The voucher enables sponsors to expedite the FDA’s review of a future drug. Instead of the conventional 10 month review timeline, the voucher indicates the FDA’s goal to complete its review of the market application within 6 months of receipt. A voucher may be sold to another drug developer to expedite the FDA’s review of its drug.^3,5

“On December 27, 2020, the Rare Pediatric Disease Priority Review Voucher Program was extended. Under the current statutory sunset provisions, after September 30, 2024, FDA may only award a voucher for an approved rare pediatric disease product application if the sponsor has rare pediatric disease designation for the drug, and that designation was granted by September 30, 2024. After September 30, 2026, FDA may not award any rare pediatric disease priority review vouchers.”⁵

The FDA also noted that, due to limited resources, should there be an influx of rare pediatric disease designation requests in the months prior to the September 30 2024 deadline, it may not be feasible to meet review timelines for all requests. Requests that are not granted by this deadline will be ineligible for a voucher “under the current provisions of the law.”⁶

Fast Track Designation

Fast track designations are intended to expedite development of therapies for serious diseases or conditions with an unmet medical need. Requests for fast‑track designation require that the indication that is the subject of the request is a serious condition and “nonclinical or clinical data demonstrate potential to address unmet medical need.” Therapies designated as “qualified infectious disease products” may also qualify for fast‑track designation.³

The designation request may be submitted with the IND submission or thereafter, but “ideally, no later than the Pre‑Biologics License (Pre‑BLA) or Pre-New Drug Application (Pre‑NDA) meeting”. Requests for fast-track designation are submitted as amendments to an open investigational new drug application (IND). The FDA determines whether the designation is granted within 60 calendar days of receipt of the request.³

Benefits of fast‑track designation include frequent communication and meeting with the Agency to discuss the sponsor’s drug development program, as well as eligibility for rolling review.³

Breakthrough Therapy Designation

Breakthrough therapy designations are also intended to expedite development of therapies for serious diseases or conditions; however, unlike fast-track designation, breakthrough therapy status requires “preliminary clinical evidence” indicating that “the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies.”³

Requests for breakthrough therapy designation may be submitted with an IND submission (as an amendment); however, it is best to request the designation “no later than the end of phase 2 meeting”. Sponsors can expect the FDA’s response to their request “within 60 calendar days of receipt of the request.”³

Although the benefits of breakthrough therapy are similar to fast-track designation, sponsor recipients of breakthrough therapy designation receive more “intensive guidance”, “organizational commitment from the Agency”, and “other actions to expedite review”. Sponsors should note that the FDA may later rescind breakthrough therapy designation status if the drug no longer meets the designation criteria.³

Accelerated Approval

The accelerated approval pathway is intended to expedite development and approval of therapies for serious conditions. The approval is “based on an effect on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict a drug’s clinical benefit.”³

To “verify and describe” anticipated clinical benefit of the therapy granted accelerated approval, postmarketing confirmatory trials are required. Both the possibility of a sponsor’s accelerated approval and the key components of a sponsor’s confirmatory trial (eg, study design and conduct) are to be discussed with the Agency during the drug’s development. When the therapy is approved, the confirmatory trial(s) should have already been underway.³

Marketing applications for therapies that have received accelerated approval will undergo a 6‑month review compared to the standard 10‑month review. Therapies approved under the accelerated approval pathway may be withdrawn if the criteria are not met.³

For questions on FDA Expedited Program Designations to Support Rare Disease Drug Developments, or regulatory strategy in general, please click here and we will connect you with the appropriate expert.

Learn more about orphan drug, rare pediatric disease, and expedited program designations by watching our full webinar on the subject here.

Additional information on the FDA’s Expedited Program Designation may be found in the Guidance for Industry, Expedited Programs for Serious Conditions—Drugs and Biologics and Rare Pediatric Disease Priority Review Vouchers Guidance for Industry