By Kim Benton
This initial post has been updated as of 10/22/2025.
The original material appears below the "Commissioner’s National Priority Voucher (CNPV) Pilot Selections Announced" section.
Commissioner’s National Priority Voucher (CNPV) Pilot Selections Announced
The Commissioner’s National Priority Voucher (CNPV) pilot has progressed from concept to announcement of the first voucher recipients in a few months. Shortly after I finished a CNPV piece for the Q2 2025 Quarter Horse, FDA on July 22nd updated the CNPV web content to include a portal for submission of requests and an updated set of FAQs.
FDA announced 9 recipients of vouchers for the CNPV pilot on October 16, 2025.
Of greatest interest to most DHCG clients will be Regeneron’s DB-OTO, dual AAV vectors intended to treat genetic hearing loss due to variants of the otoferlin (OTOF) gene. DB-OTO is the only CGT, and the only CBER-regulated product of the 9 selections.
Let’s take a look at the selections and information that I was able to find on regulatory status and plans.
FDA’s press release stated, “each recipient has a product with significant potential to address a major national priority, such as meeting a large unmet medical need, reducing downstream health care utilization, addressing a public health crisis, boosting domestic manufacturing, or increasing medication affordability with Most Favored Nation pricing.” This wording largely, but not completely, tracks with the 5 national health priorities listed on the CNPV submission portal since. Applicants must choose a single priority from the following: addressing a U.S. public health crisis, delivering more innovative cures for the American people, addressing a large unmet medical need, onshoring drug development and manufacturing to advance the health interests of Americans and strengthen U.S. supply chain resiliency, and increasing affordability. Examples of national priorities were provided on the CNPV website, FDA’s YouTube channel, and podcasts—but were not indicated to be a definitive or exhaustive list. The inclusion of “drugs to treat rare diseases or address America’s chronic disease crisis” as an example for the priority of addressing a large unmet medical need on the CNPV website suggests that most CGT under development may be eligible.
I have been concerned that the variation in wording used by FDA could result in confusion over eligibility. Furthermore, because the CNPV pilot is not a negotiated PDUFA agreement or legislation passed by Congress, the eligibility criteria and selection process are subject to change at FDA’s sole discretion. Of note, review divisions appear to have had a more active role in the selection process than was indicated on the submission portal website. The website states that “pilot program submissions will be evaluated by a senior, multi-disciplinary review committee led by FDA’s Office of the Chief Medical and Scientific Officer. The council intends to select pilot participants based on the FDA Commissioner's national health priorities and application readiness (e.g., companies who demonstrate having the ability to move forward towards a marketing application).” The press release on CNPV selections stated that “each drug review division within the FDA has been charged with nominating a product that they believe meets the stated national priority goals of the program. Sponsors can also apply and have their request reviewed by the designated review division.”
Furthermore, in a Bloomberg interview video, Commissioner Makary stated that “We’re asking the reviewers on the front line, ‘are you seeing anything that is amazing?’…If we do, we are calling the companies and we’re moving them to the front of the line.” This statement implies that FDA review teams may have had an opportunity to suggest candidates that did not apply for the CNPV pilot.
While I could not have predicted the specific choices in this initial cohort of voucher recipients, I am not surprised to see vouchers awarded for products with good odds of enabling speedy review, such as previously approved products that have submitted or will submit BLA or NDA supplements. I also expected to see selections of products with imminent submissions so that FDA will have data on the pilot as quickly as possible. Other selections align with the administration’s goal of increasing U.S. domestic manufacturing. Regeneron’s DB-OTO dual AAV product might be the most novel and the greatest test of FDA’s ability to complete review in the goal of 1-2 months from a complete submission.
Another of my concerns about the subtle shifts in the criteria and selection process is how FDA would handle a situation in which multiple competing products were under consideration for CNPV. This may be a bigger concern for drugs and classes of biologics for which development of generics and biosimilars is likely and periods of exclusivity would delay approvals of competitors. Ketamine is an example. When I saw ketamine on the selection list I initially assumed the recipient was NRx Pharmaceuticals, Inc, based on their June announcement of CNPV application for their preservative-free ketamine. There are multiple OTOF gene replacement products under development and it remains to be seen what effect Regeneron’s receipt of a CNPV may have.
FDA’s expansion of the pilot cohort from the initially planned 5 to the announced 9 selections, and statement that additional selections would be announced in the near future should be seen as encouraging for those who have applied or intend to do so. Also, the choice of Regeneron’s DB-OTO confirms that CGT for rare disease are considered eligible. I view the involvement of the review divisions in CNPV selections as generally good news for CGT developers considering applying for CNPV in the future. I had feared that CGT might get overlooked in a sea of other biologic and drug applications. The involvement of the review divisions also highlights the need to foster a cooperative relationship with the review team and ensure open communication on development plans.
I continue to hope that FDA will issue a guidance document on CNPV to document the eligibility criteria and selection process, facilitate consistent messaging, and allow public comment. Until then, DHC will continue to gather information from the various methods of FDA communications and remain ready for discussion with our clients.
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original piece from 7/12/2025 (updated 7/15/2025)
FDA’s announcement of a new Commissioner’s National Priority Voucher (CNPV) program has created a great deal of buzz. The reason is simple: CNPV proposes to reduce the typical 8-month (for priority review) or 12-month (regular review) review clock for BLA and NDA applications to 1- to 2-months. Information on the CNPV is currently limited to FDA’s press release, FAQ, and YouTube video.
CNPV comparison to Priority Review Voucher (PRV) programs
Most in the CGT field are at least somewhat familiar with the existing FDA Priority Review Voucher (PRV) programs, i.e., Rare Pediatric Disease PRV, Medical Countermeasures PRV, and Tropical Disease PRV. A good starting point is identification of the main differences between these programs and CNPV. For the PRVs, a voucher was awarded upon BLA or NDA approval of a product for an indication that met criteria specified in regulation. The PRV recipient could keep the voucher or sell it to another company. The PRV could be used to obtain FDA priority review for a product that would otherwise not qualify. The sale price of PRVs has averaged around $100 million and served as an incentive for developers to pursue approval of products for unmet medical needs.
The CNPV program focuses on shortening the review clock for a product that meets CNPV criteria. A company who receives the voucher cannot sell or transfer the CNPV. However, the CNPV would be valid with change in company ownership.
Criteria for CNPV
We identified differences in the general criteria that must be met to qualify for CNPV.
The FDA press release states that the FDA Commissioner will use specific criteria to make the vouchers available to companies that are aligned with the national health priorities of:
The FAQ states that that the FDA will establish national priorities such as, but not limited to:
Of note, the press release wording in the second bullet of “more innovative cures” is softened in the press release to “potential innovative therapies,” which could be interpreted as requiring a lower threshold of evidence. In the FAQ, the fourth bullet does not specify “increasing domestic drug manufacturing” as part of the point on national security. This is particularly interesting when considering that in the YouTube video, Dr. Makary specifically states that the CNPV program “will support U.S. drug developers who are addressing our most important U.S. national priorities, such as domestic manufacturing, as a national security issue, addressing an unmet public health need, or supporting pandemic preparedness." It is unclear if any of these differences are intentional, and if so, which of the resources should be considered authoritative.
In a media appearance, Dr. Makary stated that FDA is “including the affordability of drugs as a national priority.” Thus, drug pricing is potentially another consideration for CNPV eligibility. However, because proposed drug pricing information is not included in IND or BLA submissions to FDA and is typically not announced until market launch post approval, it is unclear how this will be factored into CNPV request evaluation.
Benefits
The benefits of CNPV include enhanced communication with FDA, ability to presubmit of portions of the data and BLA/NDA application as they become available, and a proposed approval decision within 1 to 2 months once the application is complete. The accelerated approval pathway may be used if applicable legal requirements are met.
Differences in data submission and FDA review approach
In addition to the pre-submission of portions of data, changes to the FDA review approach are proposed to achieve the review decision in 1 to 2 months. The proposal is convening “experts from FDA offices for a team-based review rather than using the standard review system of a drug application being sent to numerous FDA offices” and that “clinical information will be reviewed by a multidisciplinary team of physicians and scientists who will pre-review the submitted information and convene for a 1-day “tumor board style” meeting.” It will be a requirement to submit the chemistry, manufacturing, and controls (CMC) portion of the application and the draft labeling at least 60 days before submission of the final portions(s) of the application.
FDA acknowledges that the 1- to 2-month timeline may not be feasible in all cases and “reserves the right to extend the review window if the data or application components submitted are insufficient or incomplete, if the results of pivotal trial(s) are ambiguous, or if the review is particularly complex.”
Other points
FDA plans two categories of vouchers: product designated and product undesignated. A product designated voucher would be directed by the FDA towards a specific investigational new drug of a company. An undesignated voucher “would allow a company to use the voucher for a new drug at the company’s discretion and consistent with the program’s objectives.” We interpret an undesignated voucher scenario as a company developing multiple qualifying product candidates receiving a CNPV, and once a lead product is identified the company would apply the voucher to that program.
The CNPV program will be implemented in 2025 and in the first year a limited number of vouchers will be awarded. Vouchers will expire within two years.
Application process
The FAQ states that information will be provided in the near future on how companies “can indicate their alignment with the FDA Commissioner’s criteria to meet national priorities” and request a CNPV.
Take homes
The CNPV program combines elements of other FDA expedited review programs with novel elements and an ambitious goal of 1 to 2 months to reach a decision on BLA and NDA applications. We eagerly await an FDA guidance document or other resources to clarify the eligibility criteria, application process, and number of vouchers that will be available in the first year of the program. We are aware that at least one company has issued a press release on their submission of a CNPV request. DHC is ready to help clients explore whether the time is right to submit a CNPV request for their products.
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