Patient advocates and other stakeholders are urging FDA to make predictability and consistency the center of the agency’s rare disease approach after controversies over unexpected product rejections under now-former biologics center director Vinay Prasad, saying new leadership at the center needs to address concerns from patient advocates that recent decisions have been arbitrary or politically influenced.
“Consistency and predictability I think is the name of the game,” Julie Tierney, the former deputy director of the Centers for Biologics Evaluation and Research (CBER), said at the Food and Drug Law Institute’s annual conference Thursday (May 7); Tierney is now a principal at Leavitt Partners.
With an increased number of complete response letters issued to sponsors of cell and gene therapies over the past year, Tierney said, some sponsors have felt the CRL’s reason for the rejection was inconsistent with the earlier advice they received from FDA review staff, creating an impression that CBER’s approach is “somewhat chaotic.” That’s been enhanced, she said, by statements from FDA leadership openly commenting on products still under consideration, something previous leadership would not have done without significant legal and communications review.
FDA may already be attempting to show sponsors that its approach has stabilized.
Under Prasad, CBER rejected a blood cancer cell therapy from Pierre Fabre Pharmaceuticals and Atara Biotherapeutics, with the CRL attributing the decision to the sponsors’ reliance on a single-arm trial. The companies announced Thursday they reached an agreement with FDA to resubmit the product and the agency will now consider it on the basis of the single-arm trial.
For rare disease advocates, the treatment of single-arm trials is critical.
Cara Tenenbaum, director of regulatory affairs at the National Organization for Rare Disorders, said at the FDLI conference that messaging from FDA about the importance of rare disease flexibility is meaningless if the agency won’t accept alternatives to randomized controlled trials, like natural history studies, for small patient populations. In some cases, she said, the National Institutes of Health has worked with patient organizations on creating “irreplaceable” natural history controls that FDA won’t consider.
Stakeholders at a Friends of Cancer Research event Wednesday (May 6) echoed the concerns about CBER.
Priti Hegde, senior vice president of Gilead Sciences blood cancer spinoff Kite, said predictability, clarity and consistency in the drug review process are “critically important” for industry and need to be addressed by new FDA leadership.
At the same event, Grace Graham, FDA’s deputy commissioner for policy, legislation and international affairs, said the agency is working to hire permanent leadership at the drug and biologics centers, as well as making both hiring across the agency and retention of current staff top priorities.
George Eastwood, president of the nonprofit Emily Whitehead Foundation, which advocates to increase access to cell and gene therapies, said the rare disease community has been deeply impacted by the changes to CBER’s CGT approach under Prasad.
“The frustration is very intense,” he said, adding that rare disease advocates feel CBER is pressing for randomized controlled trials in situations where they are impractical or unethical.
Eastwood said it’s important for FDA to hire more reviewers, something Commissioner Marty Makary has been focusing on, but that staff won’t be able to implement a coherent regulatory approach without guidance from the top.
The hiring of a new CBER director, he said, provides the opportunity for “a refresh that could be quite promising.”
Katherine Szarama has been named acting director of CBER and multiple candidates are reportedly still being considered to hold the role in a permanent capacity; Bloomberg reported this week that top HHS advisor Chris Klomp is blocking Makary, who’s under significant political fire, from hiring Houman Hemmati, an ophthalmologist and pharmaceutical executive, to lead the center.
Timothy Hunt, CEO of the Alliance for Regenerative Medicine, said at the Friends of Cancer Research event the next director of CBER also needs to be more communicative with industry and ensure companies know who at the center to speak with about different issues and product areas, something he said has been an issue under Prasad.
At the FDLI conference, Tierney said she’s hopeful guidance now being released on CBER product areas like cell and gene therapies will provide a more reliable basis for sponsors’ actions than promises from leadership, but she said the center also needs a permanent leader who can communicate with stakeholders about FDA’s approach and reverse its decline in staffing numbers. She noted many other leadership roles at CBER are vacant or filled in an acting capacity.
“It’s important to have a team and not just a leader for a center,” she said.
Tierney also advised product sponsors to focus on their relationships with rank-and-file review staff, saying those employees will be at FDA longer than the current leadership.