FDA accelerated approval path needs improvement, says ICER
The FDA's accelerated approval pathway has delivered some important new medicines to patients more quickly, but it is plagued by inconsistencies and a lack of transparency.
That's the conclusion of a just-published report (PDF) from the influential Institute for Clinical and Economic Review (ICER), which suggests that patients, manufacturers, payers, and purchasers are "frustrated" by the programme's shortcomings.
Accelerated approval based on surrogate or intermediate endpoint is an option for medicines intended to treat serious conditions, as long as there is a strong biological case for the therapy and developers agree to carry out trials to verify its safety and efficacy. If that happens, the drug can be upgraded to a full approval.
"The goal of the accelerated approval pathway has always been to ensure that patients receive innovative treatments faster," said Sarah Emond, president and chief executive of ICER.
"We can point to several successes where patients have benefited from expedited access to transformative medications," she added, alluding to drugs like Novartis' Gleevec (imatinib) for chronic myeloid leukaemia (CML), MSD's cancer immunotherapy Keytruda (pembrolizumab), and antiretrovirals for HIV.
On the other hand, some accelerated approvals have been controversial, such as Biogen/Eisai's ill-fated Alzheimer's disease therapy Aduhelm (aducanumab), now removed from the market amid questions about its efficacy, and Sarepta's gene therapy for Duchenne muscular dystrophy, Elevidys (delandistrogene moxeparvovec), which has seen its use restricted due to concerns about liver toxicity.
The report lists a series of recommendations to improve the pathway, including strengthening the selection of surrogate endpoints, requiring greater use of randomised controlled trials, creating a new label alert and patient educational materials for drugs with accelerated approvals, and stricter enforcement to make sure confirmatory trials are completed.
"There are […] many instances of regulatory inconsistency, lagged development of confirmatory trial data, and access restrictions that have limited patient use," said Emond. "The policy options laid out in this paper are designed to build on the successes of the accelerated approval pathway and address the challenges that remain, in service to affordable access for patients."
ICER's review does not touch upon the FDA's recently introduced national priority review scheme, which can deliver a decision within a matter of weeks and has also attracted some debate, with critics expressing concern that the selection process is opaque, the scheme lacks statutory backing, that political appointees, rather than career regulators, are carrying out the reviews, and that recipients may be selected for political reasons.
The report also comes as the FDA has been trumpeting a new regulatory framework for personalised medicines based on a "plausible mechanism," which could see therapies authorised after testing on a tiny number of patients.
