A new program at the FDA has sped up the review of three cancer drugs and may provide opportunities to accelerate review and approval for other oncology therapies even faster than the agency’s existing expedited approval programs. But details on how drugs are selected remain murky, according to experts.

The Commissioner’s National Priority Voucher (CNPV) pilot program, initially announced this past June, guarantees that companies who receive the voucher will have their drug reviewed within 1-2 months instead of the standard 10-12 months most drugs require. The first nine recipients of the voucher, announced in October, included Revolution Medicine for its pancreatic cancer drug daraxonrasib (RMC-6236). In a phase 3 trial for pancreatic cancer survival and progression, daraxonrasib targets mutations in the RAS gene, which affect more than 90% of pancreatic tumors.

The second batch, announced on November 6, included two cancer drugs, the kinase inhibitor zongertinib for HER2 non-small cell lung cancer, which had already received accelerated approval in August, and the immunotherapy drug dostarlimab for rectal cancer.

David Chung, MD, PhD, director of Clinical Research and system chief of Multiple Myeloma at Northwell Health Cancer Institute, New York City, pointed out what he considers to be some of the current unknowns about the program.

“Whenever there’s a potential mechanism for a quicker evaluation and potential approval of a new drug or therapeutic, that sounds great,” Chung told Medscape Medical News. “But we’re not privy to how these decisions are going to be made in terms of which sponsors are going to be granted these vouchers.” 

Even after the first two batches were announced, he said “it’s still too early to make any conclusions” about how this program might affect the landscape of cancer drug approvals, clinical decision-making, or patient outcomes.

The head of a company developing cancer drugs was more optimistic about the new program.

“The way I understand this is that it will be very helpful for us,” said Maurits Geerlings, MD, co-founder, president, and CEO at NanoCell Therapeutics, Inc. in King of Prussia, Pennsylvania, whose company is developing a chimeric antigen receptor (CAR)T-cell therapy with a novel delivery system.

Several CAR T therapies have already been approved for blood cancers while CAR T for solid tumors have proved more challenging in penetrating the tumor, Geerlings said. Recent breakthroughs in reaching solid tumors, however, may make some CAR T therapies eligible for these vouchers, he suggested.

Differences From Existing Programs

Beyond the faster review time, the FDA says the program’s benefits include enhanced communication during the review process, the potential for accelerated approval, and evaluation by a multidisciplinary team in a “tumor board-style review process.” 

It’s also too early to say how much additional benefit this program offers beyond the Priority Review program for cancer drugs, said another expert interviewed by Medscape Medical News.

“Priority Review is working pretty well because it allows us to get promising drugs to patients fairly quickly despite there being promising evidence but not confirmatory evidence,” R. Donald Harvey, PharmD, a professor of hematology and medical oncology at Emory University School of Medicine in Atlanta, told Medscape Medical News. “There are ways the FDA has really engendered a desire to work with manufacturers and developers to get us to this better place.”

But a review within 6 months is not always guaranteed with Priority Review because delays can occur, noted Geerlings. And this new program appears to offer more back-and-forth communication that could remove various potential roadblocks during the review process and provide “a level of exclusivity that is very, very helpful for industry partners.” 

The biggest difference between CNPV and the FDA’s other expedited approval programs, based on the FDA’s FAQ on CNPV is that the criteria, meeting one of five “national priorities,” appears broader and possibly more flexible in interpretation than what other programs require. The FDA also notes that CNPV can be combined with existing programs.

The Accelerated Approval program allows approval of drugs for serious conditions that fill an unmet medical need based on surrogate or intermediate endpoints instead of, for example, survival endpoints since overall survival endpoints. The Fast Track program offers a rolling review but without a guarantee of any specific time frame for approval, and the Breakthrough Therapy program includes the perks of Fast Track plus consideration of a new drug application no later than the end of phase 2 trial meetings with the FDA.

Another difference of CNPV is that a voucher must be used within 2 years of it being issued while the other programs do not have explicit expiration dates. Also, a company may only submit an application for one product for a CNPV voucher whereas they might have multiple products eligible for other programs.

Uncertainty About Criteria

The criteria the FDA uses to award vouchers requires the drug or company to be “aligned with” one of five national priorities described on the program overview page. These include addressing a US public health crisis, delivering more innovative cures, addressing a large unmet medical need, on-shoring drug development to boost domestic manufacturing, and increasing affordability. When asked for additional information about criteria, the FDA referred Medscape Medical News to the online materials.

“It’s not yet clear what ‘national priorities’ means now and how things might change over time,” Chung said after seeing the list of drugs that have received vouchers.

Some experts seemed optimistic about how cancer drugs would be perceived by the current administration.

“It feels like cancer is always a priority for every administration,” Harvey said. The recent bill doubling funding of certain types of pediatric cancer research seems to bear that out for this administration as well, he continued.

Geerlings similarly pointed out that two of the criteria — innovative cures and unmet public health needs — are especially applicable to many cancer therapies, including the CAR T-cell therapy his company is working on.

“With CAR T therapy, for instance, < 15% of eligible patients actually get access to it,” he said.

Experts expressed more skepticism, though, about the FDA’s ability to follow through on such a rapid review process.

“You’d have to prioritize aggressively in terms of what you would talk about to get there,” Harvey said, and it’s unclear whether only FDA staff would be involved or whether the process would also include external reviewers or consultants to look over the statistical work, data analysis, and other technicalities that can require more time.

“Going through all of that in a day would be challenging,” Harvey said.

The most challenging part to condense is not the clinical data, Harvey said, but the more laborious and demanding Chemistry Manufacturing and Controls (CMC) data. The CMC data may be particularly complex for a lot of cancer drugs because they involve more immunotherapies or protein-based drugs that are more complicated than small-molecule oral pills, for example.

“I’m not sure it’s realistic for some of these more complicated antibody drug conjugates and some other agents out there” to be reviewed in a day, Harvey said, especially when some require detailed understanding of the cell lines used to create the agent.

For drugs with preexisting approvals, that process with likely be far easier and faster because a lot of the CMC data likely will not differ much from previous reviews.

“If you have a brand-new, first-in-class antibody drug conjugate at one end of the spectrum, that is an incredibly complicated review that’s going to take a long time,” Harvey said. “If you have the fifth PARP inhibitor, where the class is well known, maybe it makes sense.”

Chung expressed uncertainty about whether efforts channeled into this new mechanism would protract the timeline for other applications.

“If you’re trying to spread equity within healthcare,” he said, referring to equity across conditions, such as the many different cancers receiving adequate attention, “and you have only a limited number of vouchers, and you’re only going to pick a few because of manpower and ability to fast track this type of approval, that’s something that could be one of the downsides of this approach.”

Potential Clinical Benefits of the Program

Harvey suggested this program could be helpful for patients, judging from previously approved cancer drugs.

“Some of the agents that have been FDA-approved have provided weeks to months of life, which in some instances can be valuable,” Harvey said. “It might mean that we get these drugs to a proportion of individuals with cancers that are more common, and it could have a pretty big public health impact if [companies] are ready to manufacture it.”

Ultimately, Harvey thinks there’s a “low-to-moderate likelihood that companies developing new cancer drugs will go down this route,” partly because they may have concerns about something getting glossed over during a rushed review that could “bite them in a post-marketing moment.” 

“Until we see the pattern of use and distribution,” Chung said, “I don’t think we can really accurately evaluate how [this program] is going to really impact oncology research and healthcare research in a broader sense.”

Harvey reported receiving institutional research funding from AbbVie, Amgen, AstraZeneca, Boston Biomedical, Eli Lilly, Genmab, GSK, Janssen, Meryx, Pfizer, Regeneron, Sanofi, and Xencor and consulting fees from Amgen, EMD Serono, Erasca, and Genmab.

Tara Haelle is a health/science journalist based in Dallas.