The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for momelotinib for the treatment of myelofibrosis.

Momelotinib is designed to inhibit 3 signaling pathways including Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1). The Company believes that the inhibition of JAK1 and JAK2 may improve symptoms and splenomegaly, and inhibition of ACVR1 can lead to a decrease in circulating hepcidin which is elevated in myelofibrosis and contributes to anemia.

The NDA submission is supported by data from the global, randomized, double-blind phase 3 MOMENTUM trial (ClinicalTrials.gov Identifier: NCT04173494) which compared the efficacy and safety of momelotinib to danazol in 195 adults with symptomatic and anemic myelofibrosis who were previously treated with a JAK inhibitor. Patients were randomly assigned 2:1 to receive an oral daily dose of either momelotinib 200mg or danazol 600mg for 24 weeks, after which patients receiving danazol were allowed to crossover to receive momelotinib.

Results showed that patients treated with momelotinib met the primary endpoint achieving a total symptom score (TSS) response rate of 24.6% at week 24 compared with 9.2% of patients treated with danazol (P =.0095). The change from baseline in TSS was -9.36 for the momelotinib arm and -3.13 for the danazol arm (P =.0014).

Additionally, a greater proportion of patients treated with momelotinib achieved the following key secondary endpoints at week 24 compared with danazol, respectively: 

  • Transfusion independence status, defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for at least 12 weeks immediately prior to the end of week 24, with hemoglobin levels of at least 8g/dL: 30.8% vs 20.0% (one-sided P =.0064).
  • Splenic response rate, defined as a reduction in spleen volume of at least 25% from baseline: 40.0% vs 6.2% (P <.0001).
  • Splenic response rate, defined as a reduction in spleen volume of at least 35% from baseline: 23.1% vs 3.1% (P <.0006).
  • Rate of zero transfusions: 35.4% vs 16.9% (P =.0012).

As for safety, the most common treatment-emergent adverse events (TEAE) of Grade 3 or greater for momelotinib and danazol, respectively, were thrombocytopenia (22% vs 12%), anemia (8% vs 11%), and infections (15% vs 17%). The incidence of treatment discontinuation due to TEAEs were 18% in the momelotinib arm and 23% in the danazol arm.

A Prescription Drug User Fee Act action date of June 16, 2023 has been set for this application.

References

  1. US FDA accepts new drug application for GSK’s momelotinib for the treatment of myelofibrosis. News release. GlaxoSmithKline. Accessed August 17, 2022. https://www.gsk.com/en-gb/media/press-releases/us-fda-accepts-new-drug-application-for-gsk-s-momelotinib-for-the-treatment-of-myelofibrosis/
  2. Mesa RA, Gerd 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. Published online June 2, 2022. doi:10.1200/JCO.2022.40.16_suppl.7002