The FDA’s drug review process can often be “unpredictable,” and review teams typically “differ greatly” in what they ask of drug sponsors, Sen. Bill Cassidy said.
Sen. Bill Cassidy (R-LA), chairman of the Senate’s Health, Education, Labor and Pensions Committee, has identified “unnecessary bottlenecks” in the FDA’s operations—and offered suggestions that could help the regulator more efficiently bring medicines to Americans.
“One of the greatest challenges innovators face,” Cassidy wrote in an 18-page report published Wednesday, “is that the FDA’s process for reviewing products can be an unpredictable ‘black box.’” Review teams typically “differ greatly” in what they ask of drug sponsors, he added, resulting in many companies reporting that they face a “reviewer lottery.”
Such regulatory unpredictability has resulted in confusing and inconsistent feedback to companies. Last week, the FDA slapped Moderna’s mRNA flu vaccine with a refusal-to-file letter, arguing that the biotech failed to use the “best-available standard of care” in pivotal studies. Moderna, on the other hand, claimed the regulator had previously signed off on the protocol, which uses an FDA-approved vaccine as a control.
Moderna and the FDA have since reached an agreement regarding the application and the regulator has accepted an amended package for review, with a verdict expected by August.
In the same vein, Lykos Therapeutics last year similarly claimed that there was a “changing of the goal posts” when the FDA rejected its MDMA-assisted post-traumatic stress disorder drug in August 2024. CEO Rick Doblin said at the time that the biotech had filed an amendment to its application, addressing issues raised by an advisory committee and clearing up questions regarding the candidate’s efficacy and durability of response.
“Those responses from the company were not considered in this complete response letter,” Doblin said.
The FDA should take steps “to improve predictability” in its review process, Cassidy said in his report on Wednesday.
The senator from Louisiana also paid particular attention to rare diseases, noting that some 30 million Americans suffer from one of the over 7,000 conditions identified. The majority of these patients have no treatment options available to them. “New therapies face onerous regulatory requirements that can make development cost-prohibitive, discourage investment in small-population therapies, and push this groundbreaking work overseas,” Cassidy wrote.
Indeed, the space has been beset with setbacks recently, including the rejection of Disc Medicine’s bitopertin for the rare blood disease erythropoietic protoporphyria. The rebuff came after Vinay Prasad, director of the Center for Biologics Evaluation and Research, reportedly intervened in the drug’s review and expressed skepticism over its efficacy.
Other rare disease drugs recently rejected include REGENXBIO’s Hunter syndrome gene therapy, Biohaven’s glutamate modulator for spinocerebellar ataxia and Fortress and Sentnyl’s drug for Menkes disease. “Unpredictability in rare disease drug review, including across divisions and offices, creates unnecessary obstacles to investing the time and capital needed to develop these products,” Cassidy wrote in his report.
The FDA has begun to make some progress in this regard, with the agency in November last year rolling out a “plausible mechanism pathway” for drugs catering to rare diseases. Under this scheme, the FDA will consider drugs that target a well-elucidated biological pathway underpinning a particular disease.
However, drug sponsors are looking for more clarity in these guidances.
“One of the challenges we see is that as regulations, as guidances have come out, they aren’t easily implementable,” Roberta Duncan, former chief strategy officer at Arcturus Therapeutics, said last week during a panel at Advanced Therapies Week moderated by BioSpace.
Cassidy identified several other areas of improvement for the FDA, including the use of AI, the need to adopt novel clinical trial approaches and the lengthy approval process for biosimilars.
“It should be easier to make Americans healthy by empowering them with the tools and information they need to make healthy choices and live better lives,” he wrote. “Discoveries that never leave the lab help no one.” Cassidy offered the HELP committee’s support to implement the proposals.
In developing his report, which Cassidy said still constitutes “initial input” from stakeholders, the senator consulted patient advocates, academic researchers, manufacturers, the FDA itself and other relevant entities.
