Senator Bill Cassidy (R-LA), chairman of the Senate Health, Education, Labor and Pensions Committee, has released a report identifying what he describes as “unnecessary bottlenecks” in the U.S. Food and Drug Administration’s (FDA) regulatory process. In his 18-page document published Wednesday, Cassidy highlighted concerns about unpredictability in how the FDA reviews new medicines.
“One of the greatest challenges innovators face,” Cassidy wrote, “is that the FDA’s process for reviewing products can be an unpredictable ‘black box.’” He added that review teams often “differ greatly” in their requests to drug sponsors, leading companies to experience what he called a “reviewer lottery.”
Recent disputes between pharmaceutical companies and the FDA have drawn attention to this issue. Last week, Moderna received a refusal-to-file letter from the FDA regarding its mRNA flu vaccine. The agency argued that Moderna did not use the “best-available standard of care” in its pivotal studies. Moderna responded by stating that it had previously received approval for its protocol from the regulator. The two parties have since reached an agreement; Moderna submitted an amended application package, which is now under review with a decision expected by August.
A similar situation occurred last year when Lykos Therapeutics’ application for an MDMA-assisted treatment for post-traumatic stress disorder was rejected by the FDA. CEO Rick Doblin stated at the time: “Those responses from the company were not considered in this complete response letter.”
Cassidy’s report emphasized that such unpredictability creates confusion and inconsistent feedback for drug developers. He called on the FDA to take steps “to improve predictability” in its review process.
The senator also addressed challenges facing rare disease therapies, noting that about 30 million Americans live with one of more than 7,000 rare conditions—most lacking any available treatment options. According to Cassidy: “New therapies face onerous regulatory requirements that can make development cost-prohibitive, discourage investment in small-population therapies, and push this groundbreaking work overseas.”
Several recent setbacks have affected rare disease drug development. Disc Medicine’s bitopertin was rejected for treating erythropoietic protoporphyria after skepticism was raised during its review process. Other treatments recently declined include REGENXBIO’s gene therapy for Hunter syndrome, Biohaven’s candidate for spinocerebellar ataxia, and Fortress and Sentnyl’s drug for Menkes disease.
Cassidy argued: “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.”
The FDA has begun introducing changes aimed at improving predictability in rare disease approvals. In November last year, it announced a new “plausible mechanism pathway,” which allows consideration of drugs targeting well-understood biological pathways associated with specific diseases.
However, some industry stakeholders say further clarity is needed. Roberta Duncan, former chief strategy officer at Arcturus Therapeutics, commented during a recent panel: “One of the challenges we see is that as regulations, as guidances have come out, they aren’t easily implementable.”
Cassidy’s report also recommended other improvements at the FDA—such as increasing use of artificial intelligence tools, adopting novel clinical trial designs and streamlining biosimilar approvals.
“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,” Cassidy wrote. “Discoveries that never leave the lab help no one.” He offered support from his committee for implementing proposed reforms.
In preparing his report—which he described as representing initial feedback—Cassidy consulted patient advocates, academic researchers, manufacturers and officials from both within and outside government agencies.
