The odd saga of Oncopeptides' multiple myeloma drug—thriving in Europe while sidelined in the U.S.—continued Wednesday with the FDA requesting a withdrawal of the U.S. marketing authorization for Pepaxto.
The action comes as no surprise considering the agency’s oncology advisory committee rejected Oncopeptides’ interpretation of phase 3 trial results by a 14-2 margin back in September.
“We respect FDA's accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides, said in a release. “Multiple myeloma remains an incurable disease, and the treatment options for patients with triple class refractory disease will ultimately become exhausted.”
The FDA approved the drug in February 2021 under its controversial accelerated pathway, but Oncopeptides pulled it off the market eight months later after a confirmatory trial indicated it might do more harm than good.
Oncopeptides was so distraught by the results that it said at the time it was shutting down its business units in the U.S. and Europe and would return to its R&D roots. But three months later, the Sweden-based company did an about-face, saying it would seek to secure a full approval for the drug in the U.S.
In the OCEAN-3 trial, the death rate for Pepaxto was 47.6%, versus 43.4% for the control arm, which received Bristol Myers Squibb’s Pomalyst (pomlidomide). Meanwhile, the median duration of survival was 19.7 months for those on Pepaxto versus 25 months for Pomalyst.
Oncopeptides contends that a subgroup analysis from the study shows the drug can be more beneficial than Pomalyst for elderly patients and those who are at least three years removed from stem cell transplants.
But during the advisory committee session, several members blasted Oncopeptides for its “post hoc” approach, in the words of 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 contentious meeting.
In a separate statement, Oncopeptides pointed to "significant" survival result differences between Pepaxto and the comparator drug for "large and relevant patient groups."
"We will carefully consider FDA’s request, and will base our decision on what is ultimately best for the non-transplanted elderly patients with relapsed refractory multiple myeloma. We anticipate a decision to be made in Q1, 2023."
Meanwhile, across the Atlantic, regulators have accepted Oncopeptides’ interpretation of the data. In August of this year, the European Medicines Agency signed off on the drug, known there as Pepaxti. The U.K. followed suit last month.
Papaxti is approved in combination with the chemotherapy 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.