The FDA recently ramped up its efforts to streamline drug development and review when it launched the Rare Disease Framework Initiative. The initiative is part of an ongoing push that includes other ways to shorten regulatory timelines, such as the Commissioner's National Priority Voucher program and the Expedited Investigational New Drug Pilot Program.
But efforts to shave time off the approval process don’t guarantee smooth sailing for drug developers when working with regulators, according to Sahir Raoof, founder and managing partner of the early-stage fund Proximal Ventures. This is especially true after nearly two years of upheaval at the FDA.
While biotech execs can’t predict or control what’s going on inside the agency, they can de-risk their regulatory journey by communicating earlier and more frequently than they might think is necessary. Being in constant contact can also help biotech companies learn about and adapt to FDA staff turnover more quickly.
“In a potentially changing landscape, I think the most powerful tool is having a high-touch engagement model with the agency,” Raoof said.
A bumpy FDA road
The agency has cycled through three commissioners since January 2025, including a current acting commissioner and a nominee whose appointment is still pending Senate confirmation.
“As [agency turnover] happens, there tends to not be a consistent framework or set of rules and guidance for the industry to follow, which can make it very challenging to understand how the FDA will react to a specific endpoint guidance [or] specific trial protocols and frameworks,” Raoof said. “There are examples where companies were given guidance that was walked back. And then, in some cases, even that initial reversal was reversed.”
One company that faced regulatory uncertainty is Mighty Therapeutics (formerly Stealth BioTherapeutics). Its hard-won approval for the Barth syndrome treatment elamipretide came after an initial FDA rejection that “blindsided” the company because an FDA advisory panel had previously supported the drug, the company’s CEO, Reenie McCarthy, told PharmaVoice last year.
Significant hurdles can exist after approval, too, because of post-marketing study requirements, limited payer coverage for drugs hitting the market with accelerated approval and uneven clinical data.
“In a potentially changing landscape, I think the most powerful tool is having a high-touch engagement model with the agency.”
Sahir Raoof
Founder, managing partner, Proximal Ventures
Replimune finally won accelerated FDA approval for its melanoma drug Tudriqev in early August after overcoming two prior rejections and a divided advisory committee vote. Yet, the biotech’s stock slumped 11% in after-hours trading on approval day, following a volatile week in which FDA staff concerns spooked investors.
Speedier approvals also don’t promise payer coverage. An MMIT survey found 45% of payers place restrictions on expedited drugs, especially prior authorizations and step therapy restrictions. Others won’t cover them at all. Last year, Independence Blue Cross established an 18-month benefit exclusion for certain products with accelerated FDA approval, excluding cancer treatments.
“It’s possible that the evidence that the FDA was comfortable making an approval on may differ from the bar that payers may require,” Raoof said.
De-risking drugs on the accelerated path
As biotech execs attempt to navigate these hurdles, Raoof says it’s always a good idea to “overcommunicate” with the FDA. Doing so can facilitate ongoing discussions about specific primary and secondary endpoints, trial designs and inclusion and exclusion criteria, both before and after accelerated approval.
“It's making sure that there is alignment with the agency on what is required to satisfy these postmarketing commitments … to make sure that there is little to no subjectivity in what's being measured, how it's being measured [and] over what period of time it's being measured,” he said.
It’s also important to have the “regulatory strategy well-codified in advance” for any potential post-marketing study requirements, he said. That might look like enrolling patients prospectively or finding opportunities to leverage any real-world patient data that’s being collected.
“I've seen reg affairs teams or HEOR [health economics and outcomes research] teams start to pull together what a phase 4 study, a post-marketing study, or a prospective registry [might] look like post-approval in parallel or even before the registrational study data is submitted,” Raoof said.
Doing so can “get the ball rolling on getting that infrastructure stood up so that once the formal approval and any sort of PMC [postmarketing commitment] is issued to the company, there's no time lost and they can start to satisfy those requirements as quickly as possible.”
Even with these challenges, Raoof believes that successfully navigating an accelerated approval process can work if companies make sure they’re not only satisfying the requirements of the FDA, but other stakeholders like payers and prescribers.
“These are distinct tasks that a successful biotech or pharma company needs to manage to actually achieve not just a faster FDA approval, but a faster time-to-access for the right patient to get a newly approved therapy,” he said.
