Pepaxto Approved for Triple-Class Refractory Multiple Myeloma

The approval was based on data from the multicenter, single-arm phase 2 HORIZON trial.

The Food and Drug Administration (FDA) has approved Pepaxto® (melphalan flufenamide; Oncopeptides) in combination with dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody. 

Pepaxto is a peptide conjugated alkylating drug that is highly lipophilic, which allows it to be passively distributed into cells. “The compound then leverages amino peptidases that are overexpressed in multiple myeloma cells, causing the release of the cytotoxic payload,” explained Jakob Lindberg, Chief Scientific Officer at Oncopeptides.

The approval was based on data from the multicenter, single-arm phase 2 HORIZON trial ( NCT02963493), which evaluated the efficacy and safety of Pepaxto in combination with dexamethasone in 157 patients with relapsed or refractory multiple myeloma, of whom 97 were triple-class refractory and had received at least 4 prior lines of treatment. Patients received Pepaxto 40mg intravenously on day 1 and dexamethasone 40mg orally on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

Results showed an overall response rate (ORR) of 23.7% (95% CI, 15.7-33.4), of which 9.3% of patients achieved a very good partial response and 14.4% achieved partial response. The median duration of response was 4.2 months (95% CI, 3.2-7.6) and the median time to first response was 2.1 months (range: 1.0 to 6.1 months).

As for safety, the most common adverse reactions reported (incidence of greater than 20%) were fatigue, nausea, diarrhea, pyrexia and respiratory tract infection. The most common laboratory abnormalities (incidence of greater than or equal to 50%) were decreased leukocytes, decreased platelets, decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and increased creatinine.

Pepaxto is supplied in 50mL single dose vials containing 20mg of melphalan flufenamide as a lyophilized powder. The product is expected to be commercially available within approximately 2 weeks. 


1.    FDA approves Oncopeptides’ Pepaxto® (melphalan flufenamide) for patients with triple-class refractory multiple myeloma. [press release]. Waltham, MA: Oncopeptides Inc.; March 1, 2021. 

2.    Pepaxto® [package insert]. Waltham, MA: Oncopeptides Inc.; 2021.