The agency's approval of momelotinib marks the first for both newly diagnosed and previously treated myelofibrosis with anemia.
The FDA today approved momelotinib (Ojjaara; GSK) for the treatment of patients with intermediate- or high-risk myelofibrosis with anemia regardless of prior therapy, GSK announced in a press release.1 The approval comes following a 3-month extension of the review period to allow time for the agency to review recently submitted data.2
The approval of momelotinib, which inhibits Janus kinase 1 (JAK1), JAK2, and activin A receptor type I (ACVR1), was supported by data from the phase 3 MOMENTUM trial (NCT04173494) and a subpopulation from the phase 3 SIMPLIFY-1 trial (NCT01969838). This marks the first FDA approval for both newly diagnosed and previously treated myelofibrosis with anemia.1
In the MOMENTUM trial, patients with symptomatic and anemic myelofibrosis who were treated with momelotininb showed improved symptoms, spleen size, and anemia compared with patients treated with danazol.3 In SIMPLIFY-1, the agent showed noninferiority to ruxolitinib in spleen volume response at a reduction of 35% or greater, as well as improvement in transfusion dependence rates.1
“The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions,” Nina Mojas, senior vice president of oncology global product strategy at GSK, said in a news release.1 “Given this high unmet need, we are proud to add [momelotinib] to our oncology portfolio and address a significant medical need in the community. We look forward to helping improve outcomes in this difficult-to-treat blood cancer.”
The international, double-blind, randomized, controlled MOMENTUM study included adult patients with confirmed myelofibrosis (primary, post–polycythemia vera, or post–essential thrombocytopenia) who previously received an approved JAK inhibitor for a minimum of 90 days. A total of 195 patients with high- or intermediate-risk myelofibrosis were enrolled in the trial and randomized 2:1 to receive either 200 mg of momelotinib once daily (n = 130) or 300 mg of danazol twice daily (n = 65).
Total symptom score (TSS) response at week 24 was the primary end point in the study, with secondary end points including transfusion independence rates, 25% splenic response rates, change in TSS from baseline, 35% splenic response rate, and zero transfusions at week 24.
A significantly higher proportion of patients in the momelotinib arm experienced a 50% or greater reduction in TSS compared with the danazol arm (25% vs 9%; 95% CI, 6-26; P = .0095) in the 24-week randomized treatment period.
Hematological abnormalities by laboratory values were the most frequently occurring grade 3 or higher treatment-emergent adverse events (TEAEs) in both the momelotinib and danazol arms, and these included anemia (61% and 75%, respectively) and thrombocytopenia (28% and 26%). Regarding nonhematological grade 3 or higher TEAEs, the most common were acute kidney injury (3% and 9%) and pneumonia (2% and 9%).
Myelofibrosis, a rare form of chronic leukemia, leads to severe anemia and subsequent fatigue and weakness. Although the cause of myelofibrosis is unknown, JAKs are known to play a role in the disease through regulation of blood cell production.4
“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 of Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center. “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.”
1. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GSK. September 15, 2023. Accessed September 15, 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. GSK announces extension of FDA review period for momelotinib. News release. GSK. June 16, 2023. Accessed September 15, 2023. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-extension-of-fda-review-period-for-momelotinib/
3. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0
4. Myelofibrosis. Cleveland Clinic. Updated August 22, 2022. Accessed September 15, 2023. https://my.clevelandclinic.org/health/diseases/15672-myelofibrosis