Greater transparency in FDA decision-making was possibly the most common theme for stakeholders interviewed by the Institute for Clinical and Economic Review in a new report focused on strengthening the agency’s accelerated approval program.
More transparency is needed when it comes to the FDA’s accelerated approval program. That’s according to the Institute for Clinical and Economic Review.
Greater transparency in FDA decision-making was “perhaps the most common theme in interviews and discussions” conducted by the Institute for Clinical and Economic Review (ICER) in the preparation of its report, entitled: “Strengthening the FDA’s Accelerated Approval Pathway: Progress and Unfinished Business.”
Implemented in 1992, the FDA’s accelerated approval program enables speedier approval of certain treatments based on a surrogate or intermediate endpoint considered reasonably likely to predict clinical benefit. Sponsors must then conduct a confirmatory study to prove the drug’s benefit. Between 1992 and 2021, the FDA granted marketing approvals under this pathway a total of 278 times, according to the Institute for Clinical and Economic Review (ICER)—a key U.S. pricing watchdog. As of November 2024, the pathway had helped shepherd more than 200 new drugs to market.
Despite these successes, however, some people are concerned that tougher evidence standards mean fewer drugs are being approved under the pathway while others say too many drugs are approved with weak evidence and without the required confirmatory follow-up, ICER CEO Sarah Emond told Reuters on Thursday.
This statement tracks with a poll recently conducted by BioSpace, seeking input on the FDA’s efforts to balance flexibility and rigor in drug approvals. On this question, 34% of respondents said the FDA is “too inflexible,” while 23% said the agency is “too flexible.” A further 19% said the FDA is striking an appropriate balance, while 24% were unsure.
The accelerated approval program has become a particular point of contention over the past few years. ICER pointed to Biogen’s first Alzheimer’s drug Aduhelm and Sarepta’s Elevidys as examples of products approved under the pathway that have generated vigorous debate as more evidence came to light. Upon its approval in 2021, there was conjecture that the FDA may have collaborated with Biogen on the decision. Meanwhile, two teenage patients died last year after being treated with Elevidys—which was approved in 2023—sparking safety concerns.
More recently, the FDA’s refusal to approve Replimune’s advanced melanoma drug RP1—for a second time—under the accelerated pathway sparked outcry from the company, and debate in the public forum over whether that decision was appropriate.
In its report, ICER made several suggestions to improve the program, including strengthening the selection of surrogate endpoints and a requirement for advisory committees for accelerated approval reviews.
“There continues to be strong demand for better mechanisms to distinguish promising surrogate endpoints from those more likely to fail, and to incorporate outcomes that most matter to patients,” ICER noted in the report.
In terms of advisory committees, the FDA has pulled back on these over the past year. However, the Oncologic Drugs Advisory Committee will meet for the first time in nine months at the end of this month to discuss two of AstraZeneca’s cancer drug applications.
The nonprofit also identified improved transparency and accountability and strengthened oversight and enforcement as areas for continued improvement.
“To work as intended, the AA pathway requires trust among stakeholders. Although FDA is the central decision maker in AA, it cannot address the misgivings of the various stakeholders about each other’s motives,” the authors wrote. “But instances of lack of transparency and accountability in the agency’s processes and decisions regarding AA approvals and confirmatory trials are at the center of some stakeholders’ concerns.”
In order to improve trust among stakeholders, ICER said FDA decisions regarding new technologies and the rationales for making them should be made publicly accessible; decisions should be based on “evidence, reasons, and principles” that “fair-minded” individuals agree are relevant to decisions about how limited resources are shared across diverse needs; there must be a mechanism to appeal decisions that limit access; and finally, regulations must exist to ensure that the first three conditions are met.
Among these, ICER wrote, “publicity and relevance appear as gaps that can be addressed by FDA to reduce controversies about AA pathway decisions.”
Certainly, the FDA has made strides toward transparency regarding its decision making. Analysts recently told BioSpace that the agency’s new policy of publicizing complete response letters in real time is boosting accountability for pharmaceutical companies and providing more insight into the rationale behind decisions. Gaps remain, however, as redactions and the ongoing privacy of meeting minutes cut observers off from a key resource, they said. ICER highlighted this effort in its report.
