New Drug Application Accepted by FDA for Momelotinib in Myelofibrosis With Anemia

The FDA has accepted a new drug application for momelotinib for patients who have myelofibrosis with anemia, according to a press release from the drugs developer GSK.¹

The acceptance is based on results from the phase 3 MOMENTUM trial (NCT04173494), which assessed the agent vs danazol in a population of symptomatic patients previously treated with a JAK inhibitor. The trial met both primary and secondary end points of total symptom score, transfusion independence, and splenic response rate.² The Prescription Drug User Fee Act is set for June 16, 2023.

Results from the trial were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. A total of 195 patients enrolled and randomly assigned 2:1 to receive either momelotinib (n = 130) at 200 mg daily plus placebo or danazol (n = 65) at 600 mg per day plus placebo. At week 24, patients were able to crossover to the momelotinib.

At 24 weeks, 72.3% of patients in the momelotinib arm completed treatment vs 58.5% in the danazol arm, while 70.8% vs 61.5% in each respective group entered the momelotinib open-label expansion. Discontinuation of treatment was necessary in the momelotinib arm because of adverse effects (AEs; n = 16), patient decision (n = 6), insufficient efficacy (n = 6), death (n = 4), leukemic transformation (n = 2), were lost to follow-up (n = 1), or disease progression (n = 1). In the danazol arm, discontinuation occurred because of AEs (n = 11), patient decision (n = 5), death (n = 3), insufficient efficacy (n = 3), disease progression (n = 2), and leukemic transformation (n = 2), and investigator discretion (n = 1).

In terms of splenic response rate at 24 weeks, 40.0% (95% CI, 31.51%-49.95%) of patients in the momelotinib arm had a 25% reduction vs 6.2% (95% CI, 1.70%-15.01%) in the danazol arm (P <.0001). Moreover, a 35% reduction was observed in 23.1% (95% CI, 16.14%-31.28%) in the momelotinib arm and 3.1% (95% CI, 0.37%-10.68%) in the danazol arm (P = .0006). In the momelotinib arm at baseline, the transfusion independence rate was 13% and 31% at 24 weeks compared with 15% and 20% in the danazol arm, respectively (P = .0064).

AEs of grade 3 or higher were observed in 53.8% vs 64.6% and serious AEs were observed in 34.6% vs 40.0% of patients in the momelotinib and danazol arms, respectively. The most common grade 3 or higher AEs in each arm, respectively, was anemia (60.8% vs 75.4%), thrombocytopenia (27.7% vs 26.2%), neutropenia (12.3% vs 9.2%), acute kidney injury (3.1% vs 9.2%), and dyspnea (2.3% vs 1.5%).

References

1. US FDA accepts new drug application for GSK’s momelotinib for the treatment of myelofibrosis. News Release. FDA. August 17, 2022. Accessed August 17, 2022. https://bit.ly/3T7JzBE
2. Mesa RA, Gerds AT, Vannucchi A, et al. MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. J Clin Oncol. 2022;40(suppl 16):7002. doi:10.1200/JCO.2022.40.16_suppl.7002