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Pink Sheet — New Accelerated Approval Withdrawal Process More Streamlined, Marks Says

Pink Sheet — New Accelerated Approval Withdrawal Process More Streamlined, Marks Says

The withdrawal of Pepaxto, the first to use a new streamlined pathway, was much less agonizing than prior efforts to remove products that had received accelerated approval over the objections of the sponsor, according to Peter Marks, director of the US Food and Drug Administration Center for Biologics Evaluation and Research.

Marks, who was the designed FDA official in charge of the formal withdrawal of the multiple myeloma treatment, said the new process mandated by the 2022 Food and Drug Omnibus Reform Act (FDORA) moved quicker and more smoothly than the prior pathway.

“My deputy [director] dealt with another withdrawal and compared to the pain of that withdrawal and compared to the pain of a previous withdrawal, which was done by a previous director of the center for biologics, it felt like it was much more structured and smooth in terms of how it moved forward,” Marks said on 26 February during the Biopharma Congress. “Because of how it’s been laid out, all of the parties involved knew what needed to happen at the right times.”

The event was sponsored by Prevision Policy and Friends of Cancer Research.

The FDA announced on 23 February that Oncopeptides AB’s Pepaxto (melphalan flufenamide, also known as melflufen) should be removed from the market after the product’s confirmatory study did not verify clinical benefit. Available evidence also did not show that the drug was safe and effective under its conditions of use.

Pepaxto is the third product that used accelerated approval to gain market entry and then be withdrawn through FDA regulation. But it was the first to use the new expedited withdrawal process.  (Also see “Accelerated Approval: US FDA’s Hammer Falls On Oncopeptides’ Pepaxto” – Pink Sheet, 23 Feb, 2024.)

Marks said after the session that the structure in the new pathway made a difference. There were clear expectations for what would happen and it was clear who the decision-maker would be.

Not having to prepare for another hearing also helped, Marks told the Pink Sheet. He thought the process as envisioned in the statute appeared to work well.

“I’m not sure it needs much tweaking,” he said. “If it needs a tweak, it’s just a tweak, not a major overhaul.”

New Process Only Requires One Public Hearing

The new expedited accelerated approval withdrawal process was in response to complaints that removing a product from the market was time-consuming and cumbersome.

Sponsors could appeal the FDA decision and demand a public hearing, usually in front of an advisory committee, which required months of preparation. The process resembled a legal proceeding, as the FDA and sponsor made numerous filings on evidentiary and other issues.  (Also see “Accelerated Approval Withdrawals: Will Non-Oncology Indications Stop ‘Dangling’ In 2024?” – Pink Sheet, 30 Jan, 2024.)

Under the new process, the FDA must provide notice and explain the proposed withdrawal, as well as an opportunity for a meeting with the FDA commissioner or their designee.

A public hearing also can be convened, but is not required if the committee had not previously given advice on the subject.  (Also see “Accelerated Approval Reforms Give US FDA More Power And Flexibility – With Some Gaps” – Pink Sheet, 20 Dec, 2022.)

The FDA avoided the hearing with Pepaxto because an advisory committee voted in September 2022 that the benefit-risk ratio was not favorable.  (Also see “Oncopeptides’ Pepaxto Needs New Study To Identify Population That Will Benefit, FDA Panel Says” – Pink Sheet, 22 Sep, 2022.)

Indeed, the Pepaxto withdrawal process took about seven months after the agency’s formal withdrawal proposal, compared to the breast cancer claim for Genentech, Inc.’s Avastin (bevacizumab), which needed 11 months, and Covis Pharma’s pre-term birth prevention drug Makena (hydroxyprogesterone caproate), which needed about 30 months.  (Also see “Oncopeptides’ Pepaxto Withdrawal Speeds Through In 7 Months Under Expedited Procedures” – Pink Sheet, 23 Feb, 2024.)

Still Questions About Withdrawal Workload

But Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said that even though the withdrawal moved much faster than its predecessors, it still required a substantial amount of work.

Pazdur said during the Biopharma Congress that the agency conducted more than 60 meetings associated with the drug and “one has to ask themselves about judicious use of government resources here.”

“Even with the abbreviated type of withdrawal procedure … there is significant resources that are really spent by the agency in taking off these drugs,” he said. “I think the American public deserves to know how intensive this work is. Because here again, the stakes are high … and you have got to realize this, but over 60 different meetings about a single drug is a lot.”

FDA’s formal push for a Pepaxto withdrawal followed a change of heart from Oncopeptides, which had announced in October 2021 that it was withdrawing the product, just days before an advisory committee was schedule to discuss its fate. However, it reversed that decision several months later, though the product never returned to the market. ODAC rendered a negative verdict on the drug’s benefit-risk profile in September 2022, and CDER formally requested withdrawal in July 2023. Oncopeptides then filed a formal appeal.