What Happens When a PRV is Redeemed and the FDA Redlights the Marketing Application?

Executive Summary

The use of a Priority Review Voucher (PRV) provides an accelerated FDA review, but it doesn’t guarantee approval. Once redeemed, the PRV is considered “spent”, even if the FDA does not approve the application. In cases where a Complete Response Letter (CRL) is issued, the PRV cannot be reused for another submission. Companies can resubmit their marketing application addressing the FDA’s concerns, but the expedited review privilege granted by the PRV is no longer available. This highlights the strategic consideration needed when deciding to use a PRV, as it offers only one shot at a fast-tracked review.

Priority Review Vouchers (PRVs) and their benefits

When a company redeems a Priority Review Voucher (PRV), it accelerates the FDA’s review timeline for a drug application from the standard ten (10) months to just six (6) months. However, it is worth noting that, the redemption of a PRV does not guarantee the drug’s approval and neither does it guarantee a strict review within the six (6) month timeline. The FDA aims to complete its review and issue either an approval or a Complete Response Letter (CRL) within six (6) months after the 60-day filing period for new molecular entities, or six (6) months from receipt of other applications. However, this timeframe is not guaranteed, and it does not imply that approval will necessarily be granted within that period. If the FDA decides not to approve the drug during this expedited review and issues a CRL, the PRV is still considered “spent”, meaning it cannot be reused for any future applications – whether for the same drug or another.

The PRV program, initially established to incentivize the development of treatments for rare pediatric, tropical diseases and medical countermeasures, allows these vouchers to be sold or transferred between companies before they are redeemed. However, once the voucher has been applied to an application, its value is fully exhausted, even if the application results in a CRL. The expedited review is a one-time opportunity; if the FDA issues a CRL, the company must resubmit its application for further consideration, but it will no longer benefit from the PRV’s expedited timeline.

In some cases, a company that receives a CRL may be eligible for a “Class 1” resubmission review, which typically takes around two (2) months. The Class 1 review process is actually not faster than a regular review. In the Class 1 review both priority and normal review processes take about 2 months to review. Importantly, the resubmission following a CRL is handled under the FDA’s standard procedures unless it qualifies for specific accelerated categories.

This policy was recently confirmed by the FDA in response to an inquiry, which clarified that once a PRV is redeemed, it is no longer valid, irrespective of the outcome. This means that even if a drug application is rejected, the PRV cannot be reapplied to the same or any other application.

What Happens When a PRV is Redeemed and the FDA Redlights the Marketing Application?

The high value of PRVs, which often sell for hundreds of millions of dollars, underscores the significant stakes involved in their use. Companies must carefully consider the timing of redeeming a PRV to optimize the chances of approval. Since the voucher’s benefits are exhausted upon its use, the decision to redeem a PRV is a strategic move that should align with the best possible chances for success.

In conclusion, while the PRV program provides a valuable opportunity for companies to shorten the FDA’s review process, it does not guarantee approval. Once a PRV is used, its benefits are “spent” regardless of the outcome, and the company must be prepared to proceed through standard review channels if the FDA does not grant approval and/or issues a CRL. This makes the use of a PRV an important and carefully calculated decision for any drug developer.

References:

These references are critical in understanding how PRVs work and the implications of redeeming a voucher without getting FDA approval on the first try.

1.FDA Priority Review Guidelines: The PRV program operates under the same priority review process described in the FDA's Prescription Drug User Fee Act (PDUFA) guidelines. The PDUFA outlines the goal for completing priority reviews within set time frames. Reference to the PDUFA goals can be found in the official FDA guidelines at https://www.fda.gov/media/99140/download.

2.Withdrawal Process and Resubmission: If a company decides not to move forward with its application, they can withdraw their submission. A sponsor may also resubmit the same application after addressing the issues raised in a CRL, although the PRV is still considered “spent” after the initial submission. This is covered under FDA guidelines for resubmission after a CRL. Details about resubmission timelines and procedures are available at https://www.fda.gov/media/99140/download.

3.Class 1 Resubmission: In cases where a CRL is issued, a company may qualify for a "Class 1" resubmission, which has a faster two-month review period. However, this is distinct from the benefits of a PRV and is only available in certain situations: Overview of FDA resubmission classes and timelines can be found at https://www.fda.gov/media/99140/download.

4.Use and Transfer of PRVs: PRVs can be transferred multiple times before being used, but once they are redeemed, they cannot be reused, even if the application is not approved. This is clearly outlined by the FDA’s PRV program details. More information about the transferability and limitations of PRVs are defined at https://www.fda.gov/drugs/nda-and-bla-priority-review-vouchers/priority-review-vouchers.

Authors

Dr. Nana Mainoo, PharmD, MA

Chief Executive Officer at Cleracs Consulting

Email: [email protected] | Cell +1 757 401 3218

With over 16 years of experience in the healthcare industry, Nana has held key roles at Pfizer and Komodo Health and co-founded Medsfinder, a healthtech platform. As CEO of Cleracs Consulting, he specializes in regulatory strategy, focusing on orphan drug regulatory affairs. Nana holds a Doctor of Pharmacy from Nova Southeastern University, a Master of Arts from IE Business School, and certificates in Health Leadership and Finance from INSEAD and Cornell University, respectively, along with a Bachelor of Pharmacy from KNUST.

Christian Girard, MiM

Co-Founder at The PRV Fund Project

Email: [email protected] | Cell/WhatsApp: +33 667 266 092

Christian is a co-founder of The PRV Fund, an initiative focused on providing non-dilutive funding to early-stage biotech companies developing treatments for rare pediatric-onset disorders. Christian has over 30 years professional background marked by his commitment to advancing rare pediatric disease drug development, from lab bench to approval. His involvement in this sector highlights his dedication to supporting innovative therapies aimed at improving the lives of children with rare diseases. He is a graduate of ESCP Europe, an European business school.

Dr. Jean Chatellier, PhD

Partner, EVP & Managing Director at KYBORA

Email: [email protected] | Cell/WhatsApp: +33 609 102 105

Jean is a Partner and EVP at KYBORA, a global advisory firm specializing in M&A, licensing, fundraising, and strategic advisory services in biopharma. He contributed to the divestiture of Bayer’s PRV to argenx for $98M [1]. With over 24 years of experience, he has held key leadership roles, including CBO at Besins Healthcare and pivotal positions at Avadel Pharmaceuticals, Micromet (now Amgen), and Crucell (now J&J). He was the founding CEO of Avidis (now Osivax) and has worked with Nobel laureates during his postdoctoral research. Jean holds a PhD in Biochemistry and Molecular Biology and has led significant industry partnerships and transactions throughout his career.

[1] On November 2020, argenx enters into agreement to acquire Priority Review Voucher https://www.globenewswire.com/news-release/2020/11/23/2131371/0/en/argenx-Enters-Into-Agreement-To-Acquire-Priority-Review-Voucher.html.