On February 26, 2021, the FDA accelerated the approval of melphalan flufenamide (Pepaxto; Oncopeptides AB), an alkylating drug, for the treatment, in combination with dexamethasone, of adults with relapsed or refractory multiple myeloma who have received ≥4 lines of therapy and whose disease is triple-refractory to ≥1 proteasome inhibitors, 1 immunomodulatory drug, and 1 CD-38–directed monoclonal antibody.
Melphalan flufenamide is the first peptide–drug conjugate approved for the treatment of multiple myeloma. The FDA granted it a priority review and an orphan drug designation for this indication.
“Research has shown melphalan flufenamide to be a novel and innovative therapeutic option, which is active in refractory disease and has manageable toxicity, with the convenience of being administered by infusion once a month,” said Paul G. Richardson, MD, Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute. “Based on our findings, melphalan flufenamide is an important addition to the treatment armamentarium, with the potential to meaningfully improve outcomes in an area of important unmet medical need.”
The FDA approval was based on results from the multicenter, single-arm HORIZON clinical trial. Of 157 patients with relapsed or refractory multiple myeloma, 97 patients had triple-refractory disease and had received ≥4 lines of therapy. The FDA approval was based on the subpopulation of 97 patients. Patients received intravenous melphalan flufenamide 40 mg on day 1 and oral dexamethasone 40 mg on days 1, 8, 15, and 22 of every 28-day cycle, until disease progression or until unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The ORR in the subgroup was 23.7% (95% confidence interval [CI], 15.7-33.4), and the median DOR was 4.2 months (95% CI, 3.2-7.6).
The safety of melphalan flufenamide was evaluated in the total study population of 157 patients. The most common (>20%) adverse reactions were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common (≥50%) laboratory abnormalities were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.