During a meeting with acting FDA Commissioner Kyle Diamantas and other agency officials, rare disease groups discussed whether advisory committees could examine broader scientific, regulatory and development issues affecting multiple diseases more often.
Key Takeaways
- Rare disease groups urged senior FDA officials to modernize its approach to endpoints, biomarkers, trial design and evidence generation for small patient populations during a private meeting.
- Stakeholders encouraged the aency to use advisory committees to address cross-cutting scientific and policy issues that impact multiple products.
- Agency leaders acknowledged staffing and workforce capacity concerns during the meeting.
Rare disease advocates urged the US Food and Drug Administration to rethink its approach to setting clinical endpoints, validating biomarkers, designing clinical trials, reforming advisory committees and evaluating evidence in small patient populations during a meeting with senior agency leaders.
The June 3 closed-door roundtable was convened by Amy Comstock Rick, director of the FDA’s Rare Disease Innovation Hub and included Acting Commissioner Kyle Diamantas, Acting Center for Drug Evaluation and Research Director Michael Davis, Acting Center for Biologics Evaluation and Research Director Karim Mikhail and representatives from more than a dozen rare disease patient groups.
Participants described the meeting as part of the FDA leadership’s effort to establish an ongoing dialogue with the rare disease community after months of uncertainty surrounding the agency’s approach to several high-profile orphan products. Stakeholders left the meeting encouraged by the tone, but eager to see concrete action.
“It seems like it was very collaborative, and they seem to understand that they have things to learn,” one person familiar with the discussion said. “Everybody left hopeful that FDA will take action.”
Address Root Causes Of Evidence Challenges
Several participants said the discussion focused on addressing earlier regulatory decisions that determined the evidence sponsors must generate before filing applications.
A person familiar with the discussion said patient groups argued many rare disease development challenges stem from FDA expectations for endpoints, trial design and evidence generation rather than the mechanics of application review.
Two attendees said groups urged the FDA to take a more holistic approach to rare disease development, including reassessing whether sponsors should be asked to collect data on clinically meaningful endpoints and whether randomized controlled trials are accurate in very small patient populations.
Biomarker Qualification Program Draws Attention
Another major topic was the FDA’s biomarker qualification program, which several organizations said needed reform.
Jeff Allen, president and CEO of Friends of Cancer Research, who attended the meeting, said participants discussed opportunities to improve the qualification of biomarkers and novel endpoints that could support drug development across multiple rare diseases.
Allen said sponsors have long worried that biomarker qualification efforts often become stalled within the FDA.
Last year, FOCR published an analysis examining a decade of the biomarker qualification program that found only about 15% of submissions accepted into the program completed the process.
“A lot of them get stuck for an extended period of time,” Allen said.
Allen also said stakeholders discussed potential improvements, including more involvement from agency experts and streamlined review processes, as well as approaches that better accommodate the evolving nature of scientific evidence.
The discussion also covered the agency’s evolving “plausible mechanism” framework. Some stakeholders view the pathway as potentially important pathway for evaluating therapies targeting ultra-rare diseases or highly personalized patient populations where traditional evidence standards may be difficult to meet.
Expand Advisory Committee Engagement
Participants also questioned the FDA’s use of advisory committees, including whether it should return to more frequent engagement with external experts.
Allen said FDA leaders acknowledged a willingness to utilize advisory committees more frequently while also considering improvements in their structure and use.
The discussion extended beyond product-specific reviews and included advisory committees use to address scientific, policy and development challenges affecting multiple diseases.
“I think it was more whether there was an opportunity to utilize adcomms for broader topics than just a singular application,” Allen said, adding that the Oncologic Drugs Advisory Committee has been convened to discuss issues such as clinical trial design.
Participants also highlighted recurring challenges identifying experts with sufficient disease-specific expertise for rare disease advisory committee meetings.
Staffing Concerns Raised
Patient groups have closely monitored FDA staffing losses following the Health and Human Services Department’s reduction in force and voluntary departures, in part because ultra-rare disease therapies often require specialized scientific expertise.
The EveryLife Foundation for Rare Diseases said participants emphasized the importance of maintaining a strong and experienced FDA workforce capable of supporting rare disease innovation.
The organization said in a June 4 press release that stakeholders discussed preserving FDA scientific expertise and ensuring organizational changes do not disrupt regulatory programs that many rare disease developers need for guidance and review.
FDA officials did not announce any staffing initiatives during the meeting, but attendees said agency leadership appeared receptive to concerns about workforce capacity.
Agency Promises Continuing Dialogue
The meeting did not produce formal commitments or timelines for specific initiatives, but attendees said FDA leaders emphasized the discussion would continue.
Allen said agency officials are interested in creating more regular opportunities for patient group engagement and expanding participation to include division directors and review staff.
“They were pretty clear in saying that this wasn’t intended to be a singular conversation,” Allen said.
Participants viewed the presence of FDA’s acting commissioner, center directors and senior policy officials as a signal agency leadership is prioritizing rare disease issues.
However, the key test for many advocates will be translating the discussions into changes in the FDA’s approach.
Rare disease stakeholders want more regulatory certainty following several high-profile setbacks for rare disease and gene therapy products under former Commissioner Martin Makary.