FDA

Puma wins a big round in fight for neratinib OK as experts offer a crucial thumbs up

Puma Biotechnology $PBYI won a crucial vote in favor of its experimental breast cancer drug neratinib, with a majority of outside experts offering the FDA a thumbs-up vote in favor of approval as an extended adjuvant treatment.

On the key question of whether the risk/benefit profile of neratinib warranted an approval, the panel voted twelve to four in favor of the drug. But the support came with plenty of caveats about the narrow benefit the data demonstrated and questions about the drug’s often harsh impact on patients. Several panel members called on the FDA to narrow the approval to a smaller set of patients most likely to benefit.

“There’s no exclamation point after my ‘yes’,” said Andrew Seidman, an oncologist at Memorial Sloan Kettering. “It’s just a yes.” He added that he was happy that the drug looks durable and the statistical analyses applied to the data given the significant changes to the study design. “I do think that physicians will select patients very selectively for using this,” he noted, echoing a concern that the approval the company was seeking was too broad given the data available.

If it makes it to the market, those comments may come back to haunt Puma, to some extent. But today, Puma execs had plenty to celebrate. Its shares immediately shot up more than 25% after trading resumed in the early afternoon, adding to the big spike that occurred when the FDA’s written review hit on Monday.

Puma has been at the center of a roving street fight between investors going long and short on the stock. But there were none of the fireworks predicted during the review on Wednesday.

The bears’ argument that the drug triggered such serious adverse events that it would be spurned by the FDA ran into the experts’ support for the marginal benefit the drug demonstrated, improving disease-free survival in HER2 positive patients by 2.3%. About 94.2% of patients in the neratinib arm were alive without their disease progressing at two years, compared with 91.9% in the control arm.

One of the biggest issues highlighted in the FDA’s written review of the drug was that agency officials had advised Puma not to file based on the data from their pivotal trial. That didn’t seem to weigh heavily on the panel, though Puma won’t know for sure if it’s out of the woods until the FDA provides a formal decision.

Panel votes are not binding.

There were serious adverse events in the study, primarily reflected in high levels of serious, though not life threatening, cases of diarrhea. The agency’s review, though, did not raise major red flags for Puma.

“Most toxicities are nonserious and reversible,” said the FDA’s Amanda Walker, “but the true magnitude of benefit remains uncertain.”

The benefit was uncertain because of the changes Puma made to the registrational study after taking over from Pfizer. Investigators for Puma went back to reconsent patients for a longer period of review and did that with 75% of the patients, but data were still missing on 754 patients.

But why would a physician choose this drug compared to what’s already available, asked one of the panelists.

Puma consultant Jose Biselga noted the “relative risk reduction of 34% compared to what is available currently.” Would I want the option to use it? “To this I would answer ‘yes.’ I would go a long way to get this done.”


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