JPM23: Is GSK's 15-day accelerated approval withdrawal the new normal? Hear FDA Commissioner Robert Califf's response

In a surprising move, GSK recently pulled multiple myeloma therapy Blenrep off the U.S. market just 15 days after the drug flunked a confirmatory trial. The product pull came at the request of the FDA, and the company's speedy action prompted industry watchers to wonder if there's a new benchmark for removing indications under the agency's accelerated approval program.

But as FDA Commissioner Robert Califf sees it, the Blenrep case doesn’t apply to all accelerated approvals.

During an interview on the sidelines of the J.P. Morgan Healthcare Conference, Califf lauded GSK’s move as “a great sign of corporate responsibility." Still, not all confirmatory trial failures should trigger immediate product withdrawals, the FDA chief argued.

“There may be results that are just clear-cut, the thing didn’t work, but there may be patients who are taking the treatment who have concerns,” Califf said.

In recent years, the FDA has faced criticism for a lack of oversight around its accelerated approval program. The pathway allows the agency more leniency to approve drugs in diseases where patients have few or no good options, but it does require companies to complete confirmatory trials after the speedy nods.

Critics have said the agency isn't enforcing confirmatory trial requirements and that it's not forcing companies to pull their drugs from the market when products do fail these studies.

For example, Merck's Keytruda, when used as a monotherapy in third-line PD-L1-positive stomach cancer, failed confirmatory trials in late 2017 and the spring of 2019. But the FDA only publicly scrutinized the indication in 2021, leading Merck to pull the indication the same year. In contrast, GSK’s quick withdrawal sparked the attention of cancer drug developers.

In the past, the FDA has cited trial design flaws or remaining unmet medical to keep accelerated approvals in place despite confirmatory study flops. But more recently, the agency has started calling for quick withdrawals in problematic indications. The regulator generally wants more power to pull flawed indications.

“If the confirmatory study has clearly failed, then I think the companies have to step up and take these drugs off the market as rapidly as possible,” FDA’s oncology chief Richard Pazdur said during the Friends of Cancer Research annual meeting in November.

At the time, Pazdur lamented how many resources went into the FDA's battle with Roche over a breast cancer indication more than a decade ago. He called the experience a "nightmare."

“I believe very strongly we need more teeth," Califf said during the November meeting, “because once the approval occurs, it’s very difficult to hold back the marketeers.” One idea the agency has floated is a requirement that confirmatory studies are ongoing before the accelerated approval is granted

But despite this increased scrutiny, the FDA has consistently retained some wiggle room in its regulations.

The bar for obtaining an accelerated approval still depends on the indication and existing treatment options, Califf said this week at JPM. As for the timely initiation of confirmatory studies, Pazdur has told Fierce that several factors could affect the agency's final decision on accelerated nods, such as the breakthrough nature of the drug and how far along the research has progressed.