Viatris pulls decades-old accelerated approval thanks to 'unfeasible' confirmatory trial demand

The FDA has been cleaning up its act around accelerated approvals lately, pressuring companies to pull drugs that don’t meet their confirmatory trial requirements. Now, one more therapy has fallen from grace almost 25 years after its original go-ahead.

The FDA is withdrawing the accelerated approval for Mylan’s legacy antimicrobial powder Sulfamylon following a request by Mylan’s parent company Viatris, the agency said in a public filing (PDF). This is separate from a Sulfamylon cream that won approval in 1969.

Sulfamylon powder, which includes 5% sulfa antibiotic mafenide, nabbed its accelerated approval in June 1998 as an adjunctive agent to control bacterial infection when used under moist dressings over autografts on burn wounds. Before that, the drug was actually sold for decades starting in 1948, but it was taken off the market in 1971, according to the FDA’s regulatory history.

In 1998, the approval was based on a single-center, nonrandomized retrospective comparison trial looking at patient records from a hospital in Cincinnati, Ohio. Fast forward to Dec. 10, 2021, Viatris sent the FDA a letter requesting to withdraw the drug because a confirmatory study is not feasible these days, the FDA noted.

In Sulfamylon powder’s original FDA approval letter (PDF), the agency cleared a proposed Mylan phase 4 trial protocol as part of the company’s confirmatory trial commitment. At that time, Mylan was meant to conduct a randomized, evaluator-blinded, 300-subject trial comparing Sulfamylon 5% with standard-of-care in patients with 20% to 60% total body surface area burns requiring autografts.

But Mylan only started its phase 4 trial in 2007. Instead of the original agreed-upon design, the company pitted Sulfamylon against a historical control group. The company submitted the results in 2014, but the FDA “had additional modifications to the requested study,” which Mylan deemed impossible to execute, a Viatris spokesperson told Fierce Pharma on Wednesday. 

“It was deemed unfeasible to conduct such a study within the evolving clinical practice of wound control in burn patients,” the Viatris spokesperson said.

It’s not clear whether the FDA has proactively followed up with Mylan about this unresolved confirmatory trial commitment between 2014 and Mylan’s request for a withdrawal late 2021. In response to a Fierce Pharma inquiry, an FDA spokesperson said the agency works closely with all companies during the approval process but wouldn’t provide more details because those meetings are considered confidential.

RELATED: FDA wants confirmatory trials to be underway before granting accelerated cancer nods, Pazdur says

This isn’t the first time an accelerated approval has dragged over two decades without confirmatory trial results.

Takeda’s legacy Shire low blood pressure med ProAmatine, or midodrine hydrochloride, won its accelerated approval in 1996 based on data showing it can improve blood pressure. Without any confirmatory data to prove the drug can improve a patient’s ability to participate in day-to-day activities, the FDA suggested a market withdrawal in 2010.

While Shire has stopped marketing ProAmatine, its approval remains in place. And in 2019, the FDA issued a ruling that ProAmatine tablets were not withdrawn for safety or effectiveness so that it can approve generic versions of the therapy.

Viatris’ Sulfamylon withdrawal comes as the FDA has started to more actively enforce confirmatory trial requirements for accelerated approval. According to an HHS Office of Inspector General (OIG) report in September, FDA and companies withdrew 13% of all accelerated approvals, and half of the withdrawals were made since 2021.

In that report, the OIG highlighted four applications where confirmatory trial results are running significantly late, ranging from five years to nearly 12 years past their original planned completion dates.

Sulfamylon is the 12-year laggard, while Takeda’s ProAmatine and Allos Pharma’s Folotyn in T-cell lymphoma came next, with their confirmatory results 7 years and 6 years late, respectively.

Under FDA scrutiny, some large pharma companies have more quickly withdrawn their accelerated approvals after failing confirmatory trials. GSK just removed Belenrep in heavily treated multiple myeloma merely 15 days after announcing a confirmatory trial flop.