FDA Accelerated Approval of Melflufen Sought for Hard-to-treat Myeloma Patients

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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melflufen accelerated approval request

Oncopeptides has submitted a new drug application to the U.S. Food and Drug Administration (FDA) requesting the accelerated approval of melflufen (melphalan flufenamide) plus dexamethasone for hard-to-treat patients with multiple myeloma.

The application is specific for people with triple-refractory disease — those who failed to respond to at least one immunomodulatory agent (IMiD), one proteasome inhibitor, and one anti-CD38 monoclonal antibody.

It is based on data from the HORIZON Phase 2 trial (NCT02963493), in which the combination therapy was found to be safe and to lead to deep and durable responses in this patient population.

Oncopeptides is expecting to launch an Expanded Access Program (EAP) in the next couple of months, which will make melflufen available in the U.S. for myeloma patients with limited therapeutic approaches before its approval.

“I am very proud and humbled by the organizations ability to timely submit the NDA for accelerated approval of melflufen,” Jakob Lindberg, CEO of Oncopeptides, said in a press release.

“This is a major milestone for Oncopeptides and is a result of dedicated research and development activities throughout the last decade,” Lindberg said. “I would like to express my sincere gratitude to all patients, co-workers, investigators and shareholders who have provided relentless support to enable a novel treatment option for a fast-growing patient population with a significant unmet medical need.”

Melflufen is an investigational peptidase-enhanced agent that works by rapidly delivering a cancer-killing agent — an alkylating peptide – to cells. The agent only becomes fully active in the presence of aminopeptidases, which are enzymes that break down small protein fragments. These enzymes are particularly high in cancer cells.

This treatment ensures that cancer cells are targeted and destroyed, while healthy cells are spared.

The HORIZON trial is investigating the safety and effectiveness of melflufen with dexamethasone in 157 patients who had received at least two prior therapies, including one IMiD and one proteasome inhibitor, and failed to respond to treatment with Darzalex (daratumumab) and/or Pomalyst (pomalidomide).

Top-line results showed that 29% of participants responded to the combination. The response rates were similar in hard-to-treat patient subgroups, including in triple-refractory patients (26%) and in those with extramedullary disease (24%).

Compared with the overall population, the patients with triple-refractory disease also showed nearly identical duration of response (5.5 months vs. 4.4 months), and overall survival time — 11.6 months vs. 11.2 months.

Time without disease worsening or death also was similar in these two groups — 4.2 months vs. 3.9 months — and increased to 8.5 months among patients who responded to treatment in both groups.

The safety profile of the melflufen combination therapy was consistent with previous trials, without new safety concerns identified. Most patients (94%) experienced severe or life-threatening side effects, with the most common being low white blood cell counts, low platelet counts, and anemia. Fatal adverse events were reported in 10 patients, but none was linked to treatment.

An ongoing Phase 3 trial is now investigating whether the combination of melflufen and dexamethasone is superior to standard-of-care Pomalyst and dexamethasone in relapsed or refractory myeloma patients.

That study, called OCEAN, has reached its final stage of patient recruitment. It is enrolling people who received at least two prior therapies, including one IMiD and one proteasome inhibitor, and failed to respond to Revlimid (lenalidomide).

Pending positive results, OCEAN’s findings are likely to support the full approval of melflufen for multiple myeloma patients in the U.S. as well as a marketing authorization application to the European Medicines Agency.