How can two drug regulators—operating under the same guidelines—interpret a dataset in two different ways?
That’s the question that has vexed Swedish biotech Oncopeptides in its efforts to advance its multiple myeloma drug Pepaxto on both sides of the Atlantic.
While the infused treatment—which was endorsed by the FDA in February of 2021—is now off the market in the United States due to safety concerns, it is speeding its way to approval in Europe.
On Thursday, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended full marketing approval for the drug, which is known in Europe as Pepaxti.
The endorsement is a stark reversal from October of last year when Oncopeptides voluntarily pulled Pepaxto from the market after the FDA issued a safety warning on the drug and shut down its confirmatory trial. The company said it would not only pull the plug on its business units in the U.S. but would do the same in Europe and return the biotech to its R&D roots.
But three months later—bolstered by its renewed belief in the drug and after former CEO Jacob Lindberg returned to replace Marty Duvall—Oncopeptides revealed a change of heart. The company rescinded its letter to the FDA, which had effectively removed Pepaxto from the market.
“I had run a lot of clinical trials through my days. Trials fail. The experiment didn’t work, right? You have a beer over it, and you move on,” Lindberg said. “That wasn’t the case here. The whole thing felt really wrong.”
A year ago, everything was progressing nicely for newly sanctioned Pepaxto until the FDA issued a warning about its safety based on early results of a required confirmatory trial. The phase 3 Ocean study showed that patients treated with Pepaxto and the steroid dexamethasone had a 10% higher risk of death than those who receive Bristol Myers Squibb’s Pomalyst plus dexamethasone.
But the EMA has viewed the data from the same trial differently, thanks to its “willingness to look one layer deeper,” Oncopeptides’ chief medical officer Klaas Bakker said.
“EMA’s assessment of Pepaxti corroborates our scientific conclusion that the overall survival result in the Ocean study constitutes a case of true survival heterogeneity,” Bakker said. “In addition, EMA confirms that there are no toxicological safety signals and a positive benefit-risk profile in the indicated patient population.”
Lindberg and Bakker said they could not find an instance of the two regulators differing so markedly on the same product.
“To say safety warning—drug should be taken off (the market). Same dataset—full approval of confirmatory trial. It’s two different worlds, with exactly the same data,” Lindberg said. “It makes you think, ‘Wait a minute. This should be empirical-based science. It shouldn’t be possible,’ to be honest.”
The EMA will have 60 days to decide whether to accept the CHMP’s recommendation. Oncopeptides is planning a fourth-quarter launch, starting in Germany.
The company now even sees a path forward for U.S. patients as the EMA’s evaluation has “intensified” Oncopeptides’ dialogue with the FDA, it said in a release.
The company is anxious to be able to provide the drug to as many patients as possible. Its approval in the U.S. is as a fourth-line therapy, where roughly 15,000 people annually could be treated. As a third-line treatment in Europe, it could be used by 8,000 to 10,000 a year, Oncopeptides estimates.
“We are really pleased with the EMA giving us not a conditional but a full approval and also taking the Ocean study for what it is—confirming the benefit of this drug,” Bakker said. “That to us means a lot at this stage, especially given all the negative we’ve had in the U.S.”