FDA Accepts NDA for GSK Subsidiary’s Momelotinib for Treatment of Myelofibrosis

The regulatory submission includes data from the MOMENTUM phase 3 clinical trial that met all primary and key second efficacy end points.

The FDA has accepted a new drug application (NDA) for momelotinib (Sierra Oncology Inc, GSK), a medication with the potential to address unmet medical needs for individuals with myelofibrosis with anemia.1

There is Prescription Drug User Fee Act action date is June 16, 2023.1

The NDA is based on results from various phase 3 trials, including the MOMENTUM trial, which met all primary and key secondary endpoints, including splenic response rate (SRR), total symptom score (TSS), and transfusion independence (TI) rate.1

The double-blind, global, randomized clinical trial compared momelotinib to danazol in individuals with myelofibrosis who have anemia and were symptomatic. The individuals also had been previously treated with an FDA-approved JAK inhibitor.1

Investigators designed the trial to evaluate the efficacy and safety of momelotinib for treating and reducing key hallmarks of the disease, including blood transfusion because of anemia, symptoms, and splenomegaly because of an enlarged spleen.1

Individuals in the study were randomized at 2:1 to receive either danazol or momelotinib. After 24 weeks of treatment, the individuals who were on danazol were eligible to received momelotinib. Investigators confirmed that early crossover to momelotinib was available for splenic progression.1

There were 195 individuals from across 21 countries included in the trial.1

The trial’s primary efficacy endpoint was TSS reduction of at least 50% or more over the 28 days immediately before the end of week 24 compared with the baseline TSS. Investigators used the Myelofibrosis Symptom Assessment Form.1

The key secondary endpoint included TI rate for 12 weeks or longer immediately before the end of week 24 with hemoglobin levels of 9 g/dL or greater. Also, investigators included SRR based on splenic volume reduction of 35% or greater at week 24 from baseline as a key secondary endpoint.1

The primary analysis data form the MOMENTUM trial was recently presented at the 2022 American Society of Clinical Oncology Annual Meeting and the European Hematology Association 2022 Hybrid Congress.1

Momelotinib is a potential new medication with a differentiated mechanism of action with inhibitory ability along 3 key signaling pathways: Janus kinase (JAK) 1; JAK2; and activin A receptor, type 1 (ACVR1).1

Inhibition of JAK1 and JAK2 could improve constitutional symptoms and splenomegaly. Also, the direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anemia.1

GSK acquired Sierra Oncology in July 2022.

Myelofibrosis is a buildup of scar tissue in the spongy tissue inside of the bone, which could lead to anemia, fatigue, swelling of the liver and spleen, and weakness, according to the National Center for Advancing Translational Sciences.2

The National Institutes of Health estimates that fewer than 50,000 individuals in the United States have this disease.2

The common age range for symptom onset is from aged 19to 65 years.2

Reference

1. US FDA accepts new drug application for GSK’s momelotinib for the treatment of myelofibrosis. News release. GSK. August 17, 2022. Accessed August 18, 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. National Center for Advancing Translational Sciences. Primary myelofibrosis. NIH. Updated November 8, 2021. Accessed August 18, 2022. https://rarediseases.info.nih.gov/diseases/8618/primary-myelofibrosis