Oncopeptides' Pepaxto reaches end of the line in US after FDA yanks approval

Following a contentious advisory committee meeting and an FDA request for the withdrawal of Oncopeptides’ multiple myeloma drug Pepaxto from the U.S. market in late 2022, the other shoe has dropped.

The FDA has determined that the grounds for pulling the drug’s approval have been met, Oncopeptides revealed in a press release Friday.

Oncopeptides’ next steps are to “thoroughly assess the decision,” which it previously appealed, and maintain its focus on commercialization in the European Union, where its drug boasts full marketing authorization under the name Pepaxti.

Pepaxto was approved in the U.S. in February 2021 under the FDA’s accelerated pathway. Oncopeptides subsequently removed the drug from the market eight months later after a confirmatory trial put Pepaxto’s risk-benefit profile into question.

In the phase 3 OCEAN study, more patients on Pepaxto and the steroid dexamethasone died versus the control group, which received Bristol Myers Squibb’s Pomylast and dexamethasone.

At the time, Oncopeptides argued that a subgroup analysis from the study suggested Pepaxto could have an edge over Pomylast in elderly patients and those who were at least three years removed from stem cell transplants.

After threatening to shut down its U.S. and European business units and return to its R&D roots, Oncopeptides ultimately decided to seek full approval for the drug using that subgroup rationale in January 2022.

In response, the FDA summoned a meeting of outside experts, during which several members blasted Oncopeptides for its “post hoc” approach, according to FDA oncology czar Richard Pazdur, M.D.

“When you have people resubmitting data and changing analysis, this could bring up issues of study conduct and integrity of the study,” Pazdur said during the meeting.

The FDA’s oncology advisory committee ultimately rejected Oncopeptides’ interpretation of the phase 3 trial results by a 14-2 margin. The FDA afterward requested the withdrawal of the medicine.

Meanwhile, Oncopeptides’ drug is faring better overseas, where the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) endorsed a full marketing approval back in June of 2022.

Known as Papaxti across the pond, the drug is approved in combination with dexamethasone as a fourth-line treatment for multiple myeloma patients whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent and one anti-CD38 monoclonal antibody. Patients also must be at least three years removed from stem cell transplantation.

The drug also won approval in the United Kingdom in November of 2022.