FDA Approves Momelotinib to Treat Myelofibrosis Patients With Anemia

The FDA has approved momelotinib (Ojjaara) to treat intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adult patients with anemia.¹

Momelotinib is a once-daily, oral Janus kinase (JAK) 1, JAK 2, and activin A receptor type 1 (ACVR1) inhibitor. Momelotinib is now the only approved drug for newly diagnosed and previously treated myelofibrosis in patients with anemia.

The drug addresses the key manifestations of the disease, such as anemia, constitutional symptoms, and splenomegaly. Further, the direct inhibition of ACVR1 can produce a reduction in circulating hepcidin, which is increased in patients with myelofibrosis and can contribute to anemia.

“The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions,” said Nina Mojas, senior vice president, Oncology Global Product Strategy, GSK, in a press release.¹ “Given this high unmet need, we are proud to add Ojjaara to our oncology portfolio and address a significant medical need in the community.”

Myelofibrosis is a blood cancer associated with 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. The common age range for symptom onset is from 19 to 65 years. Approximately 40% of patients have moderate to severe anemia at the time of diagnosis, and most patients are projected to develop anemia over the course of the disease.²

Patients with myelofibrosis with anemia have limited treatment options and frequently require transfusions, with more than 30% discontinuing treatment because of anemia.​ Those who are dependent on transfusions typically have a poor prognosis and reduced survival.¹

The approval of momelotinib was supported by data from the pivotal, double-blind, global, randomized, MOMENTUM trial and a subpopulation of patients with anemia from the SIMPLIFY-1 phase 3 trial. MOMENTUM compared momelotinib to danazol in individuals with myelofibrosis who have anemia and were symptomatic. Patients also were previously treated with an FDA-approved JAK inhibitor.³

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 and splenomegaly because of an enlarged spleen. A total of 195 patients from 21 countries were included in the trial. Patients were randomized 2:1 to receive either danazol or momelotinib. After 24 weeks of treatment, patients who were on danazol were eligible to receive momelotinib. Early crossover to momelotinib was also available for splenic progression.³

The MOMENTUM trial achieved all primary and key secondary endpoints, with a statistically significant splenic response rate (SRR), total symptom score (TSS), and transfusion independence (TI) rate.³ 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. 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.

“With momelotinib we have the potential to establish a new standard of care for myelofibrosis patients with anemia,” said Ruben A. Mesa, MD, FACP, president and executive director, Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, in a press release.¹ “Addressing key manifestations of myelofibrosis, including anemia, constitutional symptoms and splenomegaly, makes a significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease.”

SIMPLIFY-1 analyzed the efficacy and safety of momelotinib compared with ruxolitinib in patients with myelofibrosis who were not previously treated with a JAK inhibitor. The trial’s safety and efficacy results were based on a subset of patients with anemia.¹ The efficacy of momelotinib treating patients with myelofibrosis in SIMPLIFY-1 was based on spleen volume response with a decrease by 35% or more.

In clinical trials, the most common adverse events were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.

“We are thrilled to see momelotinib reach the clinic, giving patients and their physicians another option to help manage myelofibrosis,” said Kapila Viges, chief executive officer, Myeloproliferative Neoplasms Research Foundation, said in a press release.¹ “Any new treatment that takes steps toward unlocking the mysteries of this complex and chronic blood cancer represents great progress for the field.”

References

1. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. GSK. News release. September 15, 2023. Accessed September 18, 2023. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia/

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

3. 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/