Momelotinib Improved Anemia Measures, Spleen Response, and Overall Safety Among Patients With Myelofibrosis

Results from the Double-Blind Phase 3 MOMENTUM Trial

According to findings from the phase 3 MOMENTUM trial recently published in The Lancet, momelotinib, a first-class JAK1 and JAK2 inhibitor, improved anemia measures, spleen response, and overall safety among patients with myelofibrosis compared to other JAK inhibitors. 

Previous research has indicated that, unlike other Janus kinase (JAK) inhibitors, momelotinib has shown anemia benefits in myelofibrosis. In order to further this research, Srdan Verstovsek, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors “aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator danazol in JAK-inhibitor-exposed, symptomatic patients with [anemia] and intermediate-risk or high-risk myelofibrosis.” The primary endpoint was an evaluation of the total symptom score (TSS) response rate at 24 weeks, according to the Myelofibrosis Symptom Assessment Form (MFSAF). 

195 patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis were enrolled in this study and randomized 2 to 1 into the momelotinib arm (n=130) or the danazol arm (n=65). Within the 24-week treatment period, patients in the momelotinib arm received 200 mg of momelotinib once daily plus danazol placebo. Patients in the danazol arm received 300 mg of danazol twice daily plus momelotinib placebo. 

Results indicated that 25% of patients in the momelotinib arm (n=32) reported a reduction in TSS ≥ 50%, compared to 9% of patients in the danazol arm (n=6). The most frequent grade ≥ 3 treatment-related adverse events across groups were anemia (61% in the momelotinib arm vs 75% in the danazol arm) and thrombocytopenia (28% in the momelotinib arm vs 26% in the danazol arm). Across both arms, the most frequent grade ≥ 3 non-hematological treatment-related adverse events were acute kidney injury (3% in the momelotinib arm vs 9% in the danazol arm) and pneumonia (2% in the momelotinib arm vs 9% in the danazol arm). 

As endpoints were met, Dr Verstovsek et al concluded, “Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, [anemia] measures, and spleen response, with [favorable] safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with [anemia].”

Source: 

Verstovsek S, Gerds AT, Vannucchi 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:https://doi.org/10.1016/s0140-6736(22)02036-0