New Rare Disease Framework to Rely on Early Patient Engagement
FDA's developing rare disease regulatory framework could make early patient engagement an essential part of drug development, rather than an activity primarily associated with advisory committee meetings and later stages of regulatory review, according to CBER director Karim Mikhail.
Speaking at a 10/16 Reagan-Udall Foundation meeting, Mikhail said FDA already conducts patient listening sessions and other engagement activities, but sponsors do not necessarily consider them an integral part of their development programs. "We're trying to make sure that in the future, the framework would make these, honestly, a true essential part of the process," Mikhail said. Asked whether he expected sponsors, as well as FDA, to contribute to earlier patient engagement, Mikhail responded affirmatively.
The comments provide additional insight into FDA's recently announced Rare Disease Framework Initiative (see earlier story), which is intended to establish a fit-for-purpose regulatory approach to rare disease therapies, including greater flexibility in clinical development, earlier engagement with patients and external experts, and reconsideration of certain chemistry, manufacturing and controls requirements.
The initiative acknowledges the agency’s long-used regulatory flexibility and targeted programs to support innovation in developing drugs and biologics for rare diseases. But, with only about 5% of rare conditions having an FDA-approved treatment, the agency agrees with patients, drug developers, and providers that more must be done to speed the development of safe and effective treatments for rare diseases.
Mikhail said patient perspectives are particularly important for cell and gene therapies because patients' willingness to accept treatment risks may change substantially as their diseases progress. FDA should consider those differences throughout development rather than relying on patient testimony at a single point in the regulatory process, he said. He also advocated earlier consultation with outside experts, particularly for ultra-rare conditions in which only a handful of specialists may have extensive knowledge of a disease.
Mikhail said FDA must reconsider what clinical evidence can realistically be generated in very small patient populations while maintaining scientific rigor and appropriate safety standards. "We need to think of what is the attainable evidence within what we have," he said.
CDER director Michael Davis agreed that patient input should influence clinical development before sponsors have completed trials and made substantial investments in their programs. Davis also disclosed that FDA plans to establish four internal workstreams to recommend changes to agency procedures, external communications and stakeholder engagement as the new framework is developed.
He said FDA wants input from reviewers, sponsors and patient organizations on when patient perspectives would be most useful, including during endpoint development, outcome-measure selection and clinical trial design.
The framework remains under development, and the officials did not announce specific new requirements for sponsors.