sNDA Looming After Melfufen Shows Non-Inferiority to Pomalidomide for R/R Multiple Myeloma

Melflufen flufenamide (melflufen/Pepaxto) has been deemed non-inferior to pomalidomide (Pomalyst) for the treatment of relapsed/refractory (R/R) multiple myeloma (MM), according to a press release by Oncopeptides AB.

Judgement of the agent’s non-inferiority when compared with pomalidomide was based on results from the phase 3 OCEAN study (NCT03151811). The company plans to submit a supplementary new drug application to the FDA in the fourth quarter of 2021 based on the results of the study.

"The efficacy and safety data from the OCEAN study are very encouraging, and the results will be of importance in physicians´ treatment decisions for patients with relapsed and refractory multiple myeloma,” said Pieter Sonneveld, MD, PhD, professor of hematology at the Erasmus University of Rotterdam, and principal investigator of the OCEAN study in a press release. "Melflufen has a unique mode of action, which in addition with its tolerability profile, makes the drug an attractive treatment option for many patients."

The phase 3 OCEAN study has an actual enrollment of 495 patients. The primary outcome of the study is progression-free survival (PFS) from time of randomization to time to progression, up to 24 months after the end of treatment. Secondary outcomes include, overall response rate (ORR) up to 24 months, duration of response (DoR), overall survival (OS), and safety and tolerability.

Participants were randomized into 1 of 2 arms. In arm A, patients received a combination of melflufen and dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle. Patients are treated until confirmed progression, inacceptable toxicity, or the patient or investigator decides it is not in the patient’s best ineptest to continue. In arm B, patients received 4mg of pomalidomide on days 1 to 21 and 40 mg of dexamethasone on days 1, 8, 15, and 22 of each 28-day cycles. Treatment was continued until the same circumstances as in arm A.

In order to participate, patients must be 18 years of age of older, have a prior diagnosis of MM with documented disease progression, have measurable disease, have received 2-4 prior lines of therapy, a life expectancy of 6 months or greater, an ECOG score of 2 or less, be able to take antithrombotic prophylaxis, and must have or be willing to have an acceptable central catheter. Patients with primary refractory disease, evidence of mucosal or internal bleeding, or platelet transfusion refractory, any medical condition that would expose the patient to excessive risk, prior exposure of pomalidomide, known intolerance to IMiDs, a known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization, or serious psychiatric illness are not eligible to participate.

According to an independent review committee assessment, melflufen was non-inferior to pomalidomide. PFS was 41% higher for melflufen than pomalidomide with a hazard ratio of 0.817 favoring melflufen. Additionally, the ORR for melflufen was 32.1% compared to the 26.5% for pomalidomide. Both agents had a similar discontinuation rate for adverse events (AEs) and the safety profile for melflufen was consistent with previous studies.

"The outcome from the phase 3 OCEAN study is very good news for patients with relapsed refractory multiple myeloma", says Klaas Bakker, MD, PhD, executive vice Ppesident and chief medical officer at Oncopeptides, in a statement. "This head-to-head-comparison was a bold study with an optimal design for demonstrating melflufen's true isolated treatment effects. I am truly looking forward to sharing these data with a broader audience, as the OCEAN data clearly show that melflufen may be an important therapeutic option for the increasing number of patients who need more treatment alternatives."

The news follows a recent accelerated approval granted by the FDA the melflufen in combination with dexamethasonefor the treatment of adult patients with R/R MM who have received at least 4 prior lines of therapy and is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. Melflufen was also granted approval last year for the treatment of adult patients with multiple myeloma that is refractory to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

_REFERENCE:

_{Phase 3 OCEAN study demonstrates that melflufen is at least as efficacious as pomalidomide, the most used medicine in relapsed refractory multiple myeloma. News release. Oncopeptides AB. May 25, 2021. Accessed May 27, 2021. https://bit.ly/3vykcNe.}