On September 15, the U.S. Food and Drug Administration (FDA) approved momelotinib (Ojjaara) for the treatment of intermediate- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.
Momelotinib is a once-a-day, oral Janus kinase (JAK)1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. To date, it is the only approved agent for both newly diagnosed and previously treated patients with myelofibrosis and anemia that addresses the key manifestations of the disease, namely anemia, constitutional symptoms, and splenomegaly.
Myelofibrosis affects approximately 25,000 patients in the United States and can lead to severely low blood cell counts, including anemia and thrombocytopenia; constitutional symptoms such as fatigue, night sweats, and bone pain; and splenomegaly. About 40% of patients have moderate to severe anemia at the time of diagnosis of myelofibrosis, and nearly all patients are estimated to develop anemia over the course of the disease. Physicians have had limited treatment options for patients with both myelofibrosis and anemia; these patients often require transfusions, and more than 30% will discontinue treatment because of their anemia. Additionally, patients who are transfusion-dependent have a poor prognosis and shortened survival.
MOMENTUM and SIMPLIFY-1 Trials
The FDA approval of momelotinib is supported by data from the pivotal MOMENTUM study (ClinicalTrials.gov identifier NCT04173494) and a subpopulation of adults with anemia from the SIMPLIFY-1 phase III trial (NCT01969838).
MOMENTUM was designed to evaluate the safety and efficacy of momelotinib vs danazol for the treatment and reduction of key manifestations of myelofibrosis in an anemic, symptomatic, JAK inhibitor–experienced patient population. The MOMENTUM trial met all its primary and key secondary endpoints, demonstrating statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in patients treated with momelotinib vs danazol. Results from the 24-week treatment period were presented at the 2022 ASCO Annual Meeting (Abstract 7002) and subsequently published by Verstovsek et al in The Lancet.
Co–principal investigator of the MOMENTUM trial Ruben A. Mesa, MD, FACP, President and Executive Director of Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, commented: “With momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia. 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 was designed to evaluate the efficacy and safety of momelotinib vs ruxolitinib in patients with myelofibrosis who had not received prior JAK inhibitor therapy. Safety and efficacy results for SIMPLIFY-1 were based upon a subset of patients with anemia.
In these clinical trials, the most common adverse reactions in patients receiving momelotinib were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
Kapila Viges, Chief Executive Office of the MPN (Myeloproliferative Neoplasms) Research Foundation, said: “We are thrilled to see momelotinib reach the clinic, giving patients and their physicians another option to help manage myelofibrosis. Any new treatment that takes steps toward unlocking the mysteries of this complex and chronic blood cancer represents great progress for the field.”
