OCEAN Trial Fails to Support Pepaxto for RRMM, FDA Panel Finds
In 14-2 vote, Phase 3 study findings not seen to benefit advanced patients
An advisory panel to the U.S. Food and Drug Administration (FDA) has overwhelmingly decided that the Phase 3 OCEAN clinical trial did not provide sufficient evidence to support Pepaxto (melphalan flufenamide) as a treatment for relapsed or refractory multiple myeloma (RRMM).
Notably, while the FDA will consider the committee’s suggestions in its determinations, it is not bound to abide by its vote. The agency will make a final decision on Pepaxto once all reviews are finalized, according to a press release from Oncopeptides, the therapy’s maker.
Pepaxto is designed to deliver a toxic agent to cancer cells with high levels of certain proteins called aminopeptidases, killing the cancer cells while sparing healthy cells. The therapy was recently approved for heavily treated RRMM in the European Union, where it is marketed as Pepaxti.
The FDA granted Pepaxto accelerated approval in 2021 — a process whereby the FDA can permit marketing of a therapy based on early signs of clinical efficacy, while requiring the therapy’s makers to conduct additional tests to prove the treatment is effective. Under accelerated approval, Pepaxto was indicated to treat RRMS patients who had failed to respond to at least four prior lines of therapy.
Aiming to confirm the therapy’s efficacy, Oncopeptides sponsored the Phase 3 OCEAN trial (NCT03151811) that compared Pepaxto to Pomalyst (pomalidomide) in RRMS patients with two to four prior lines of treatment. All patients were also treated with the steroid dexamethasone.
Variability may be factor in Pepaxto trial’s results
Results showed that the average time to disease progression was slightly longer with Pepaxto than Pomalyst — 6.9 and 4.9 months, respectively — but the difference was not statistically significant. The median overall survival time also did not differ significantly, though it was shorter with Pepaxto than Pomalyst (19.7 vs. 25 months).
Based on these results, Oncopeptides voluntarily withdrew Pepaxto from the U.S. market in late 2021. The company rescinded this decision in January, although it is still not marketing Pepaxto in the U.S.
According to Oncopeptides, substantial heterogeneity (variability) in OCEAN and similar studies likely affected the results. Pepaxto treatment appeared to improve survival for older patients, whereas Pomalyst had more of an effect in younger individuals.
The FDA’s Oncologic Drugs Advisory Committee (ODAC), a team of over a dozen experts in cancer and other myeloma-related fields of medicine, met to discuss these data.
“The heart of the ODAC discussion was focused on the highly heterogenous survival result in OCEAN across patient groups and how to interpret the subgroup data considering the [overall survival] result,” said Jakob Lindberg, CEO of Oncopeptides.
After discussions, the committee voted on the following question: “Given the potential detriment in overall survival (OS), failure to demonstrate a progression-free survival (PFS) benefit, and lack of an appropriate dose, is the benefit risk profile of melphalan flufenamide favorable for the currently indicated patient population?”
Of the committee’s 16 members, all but two voted “no.”
“We still have confidence in our science and data,” Lindberg said. “One day I believe that OCEAN may be recognized as the canary in the coal mine for immunomodulatory drugs that in our view is the main cause behind the [overall survival] heterogeneity and dissociation between [progression-free survival] and [overall survival] in OCEAN and show that Pepaxto has the potential to become a meaningful treatment option for elderly patients with RRMM.”