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Pink Sheet – US FDA Advisory Committees’ Future: Drug-Agnostic Panels, More Debate Time

Pink Sheet – US FDA Advisory Committees’ Future: Drug-Agnostic Panels, More Debate Time

US Food and Drug Administration Commissioner Robert Califf wants advisory committees spending more time debating drug development topics that apply to multiple products, rather than the typical product-specific events.

Some top FDA career professionals championed the idea along with Califf, who endorsed it during the 13 February Prevision Policy/Friends of Cancer Research Biopharma Congress, as the agency is undertaking a revamp of its advisory committee system. (Also see “US FDA’s Califf Expects Advisory Committee Reform Talk ‘About A Year From Now’” – Pink Sheet, 29 Apr, 2022.)

“It’s the way it used to be, and I think we need to get back to more of that,” said Califf, when asked whether more committee meetings focusing on big picture issues rather than individual applications would be better.

“We have these big societal issues and the decision about an individual product is like the tip of the spear of something that needs context,” he said. “And I think the best use of advisory committees is to get context, not the specifics on that particular product.”

Issue-oriented meetings may shift the public’s focus away from committee vote counts and whether the FDA and its advisors agree on approval decisions, Califf said. He argued that the purpose of the meetings is “not to produce gladiator votes,” but to get more nuanced advice.

“I think the best advice really is not should this drug be approved or not,” Califf said. “That decision is made by full-time civil servants. The advice is about where is the field, what’s important, what matters. And I think we need to do more of that.”

As part of the process, Califf hopes the FDA can “create the space” for panels to have more comprehensive discussions.

“I feel like often the time is too compressed, the right experts may not be in the room,” he said. “The discussions don’t actually get to the point where everybody on the committee is fully informed and then a vote is taken, and people talk about the vote. So, I think we need to fix that because the public deserves open-air discussions about what the FDA is thinking and the people that work inside the FDA deserve good advice.”

Califf acknowledged the FDA has not yet found any obvious solutions to facilitate more extensive committee debate, but said agency officials continue to work on the topic.

Califf’s comments came a week after the agency hosted an Oncologic Drugs Advisory Committee to discuss the adequacy of GSK plc’s clinical development program for Jemperli (dostarlimab) in rectal cancer. (Also see “GSK’s Clinical Development Plan For Jemperli In Rectal Cancer Draws US FDA Concerns” – Pink Sheet, 7 Feb, 2023.) The agency sought advice on both the design of the sponsor’s studies for an accelerated approval and on its plan to verify clinical benefit in what would be a precedent-setting development program. (Also see “GSK’s Phase II, Single-Arm Trial For Jemperli In Rectal Cancer Gets Panel Nod” – Pink Sheet, 9 Feb, 2023.)

Float All Boats

At the panel before Califf’s appearance at the meeting, FDA Oncology Center of Excellence Deputy Director Paul Kluetz was asked whether the agency expects to conduct more of these types of advisory panels, which would allow public debate and head off potential issues with an accelerated approval early in development, before pivotal studies are conducted.

“When we have a situation that’s so different. That advisory committee is such an important tool,” said Kluetz, who emphasized the value of bringing unprecedented situations like with Jemperli to a public setting.

“I think we should do more advisory committee meetings that are not about an individual situation, but a whole other kind of paradigm,” Kluetz added. “We’ve done it before in metastasis-free survival in non-metastatic prostate cancer. We did some other ODACs like that.” (Also see “Metastasis-Free Survival Endpoint Spreads To Labeling With US FDA Approval Of J&J’s Erleada ” – Pink Sheet, 14 Feb, 2018.)

Center for Biologics Evaluation and Research Director Peter Marks also suggested a role for advisory committees to help determine appropriate gene therapy trial designs, saying the FDA can get the most from the meetings when multiple drug development programs are likely to benefit from the conversation.

“The place where advisory committee meetings help is when you have multiple companies in the field, where a public discussion helps, essentially can potentially help float all boats,” Marks said at the Prevision Policy meeting. “And so there I think it’s more helpful than when we have one small development program around one rare disease.”

The US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices also decided to focus on broader issues after the COVID-19 pandemic caused a substantial increase in meetings on vaccine-related issues.  (Also see “With Many More COVID-19 Vaccine Changes Ahead, ACIP Expecting Fewer Public Meetings” – Pink Sheet, 7 Jan, 2022.)

Some ‘Gladiator Votes’ Needed

However, individual drug-focused meetings close to a user fee date likely will not completely disappear.

“Now, there are times when the data are unclear, and a decision has to be made. And that’s where I think the more I call it gladiator-style event can occur,” Califf said. “We need both.”

Califf also was adamant that FDA-advisory committee disagreement is not necessarily a bad thing and should at times be expected.

“If we always agreed with the advisory committee, why would you want them to meet? There’s no reason for them to do that,” Califf said.

Califf also does not seem interested in strengthening conflict of interest policies governing who can sit on the panels, seeming more frustrated with the time spent dealing with the policy than the harm the conflicts might pose.  (Also see “US FDA Advisory Committee Reboot (Part II): The Right Balance For Conflicts Of Interest” – Pink Sheet, 29 Jun, 2021.)

“If we think about rare diseases as an example, show me an expert in a rare disease who’s not spending time working on therapeutics for that disease,” Califf said 10 February during an Alliance for a Stronger FDA webinar. “Then you automatically have what traditionally is a conflict. Yet, if you look inside the FDA, the main thing that employees want out of advisory committees is expert opinion from the outside. There’s also value, of course, in the patient perspective and non-expert opinion people, people that are general experts, but all of these things need to be melded together I think in a much better way.”

As for when some of these meetings might return to in-person events after years of virtual COVID-19-era sessions, Califf seemed interested in bringing some back to the agency’s headquarters, but also said the decision rests with the individual center directors. (Also see “Inside US FDA’s Return To In-Person Meetings” – Pink Sheet, 1 Feb, 2023.)

Sue Sutter and Derrick Gingery contributed to this report.