Findings from the MOMENTUM phase 3 study show that the use of momelotinib significantly impacts patients with myelofibrosis.
Treatment with momelotinib showed clinically significant improvements over the use of danazol for patients with anemia and intermediate-risk or high-risk myelofibrosis, according to findings published in The Lancet.1
These data come from the international, double-blind, randomized, controlled, phase 3 MOMENTUM (NCT04173494) study, which found that 25% of patients in momelotinib arm (n = 130) reported a 50%, or more, reduction in patient’s Myelofibrosis Symptom Assessment Form Total Symptom Score (TSS) compared with 9% in the danazol arm (n = 65). This was a proportion difference of 16%, which researchers deemed statistically significant (95% CI, 6–26; P = .0095).
These results extended to a reduction in patient’s spleen size with 25% of patients on momelotinib responding after 24 weeks of therapy. Moreover, this arm of patients required fewer blood transfusions than compared with patients on danazol.
“Current options for managing anemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” said study lead Srdan Verstovsek, MD, PhD, professor of Leukemia at the MD Anderson Cancer Center, in a press release regarding the initial findings of the trial.2 “The trial results suggest that momelotinib is safe, well-tolerated and can improve 1 of the most common and debilitating clinical problems for this patient population.”
A total of 195 patients were randomly assigned 2:1 to either the momelotinib group (67%) or danazol group (33%) and given the study treatment for 24 weeks. Patients were given 200 mg of momelotinib orally once per day along with placebo or given 300 mg of danazol orally twice a day along with placebo.
Eligible patients were those 18 years or older with a confirmed diagnosis of primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythaemia myelofibrosis. Sixty-three percent of patients were male while 37% were female, and the median age of patients in the treatment arm was just 2 year younger than the control group at 71 years of age compared with 72 years of age.
For these patients, the researchers found that the safety profile of momelotinib was tolerable compared with previous trials and had a better profile compared with danazol. The most frequent grade 3 or higher treatment-emergent adverse events (TEAEs) with momelotinib vs danazol were hematological, which included anemia (61% vs 75%) and thrombocytopenia (28% vs 26%). The most frequent non-hematological grade 3 or higher TEAEs with momelotinib vs danazol were acute kidney injury (3% vs 9%) and pneumonia (2% vs 9%).
“If approved, momelotinib could offer an effective option for patients with myelofibrosis to improve anemia, splenomegaly and other disease-related symptoms over other approved medications so far,” Verstovsek explained in the press release. “Momelotinib may also be an ideal partner for combinations with other investigational agents in development to further control myelofibrosis symptoms.”
The ACVR1/ALK2 and JAK1/2 inhibitor initially had its new drug application accepted by the FDA after the MOMENTUM trial had met all its primary and secondary end points of reducing patient’s TSS score and having a tolerable safety profile.3 Patient follow-up is ongoing with this group, and researchers are still monitoring long-term survival outcomes with this therapy.
1. Verstovsek S, Gerds AT, Vannucchi AM, et al; MOMENTUM Study investigators. momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023 Jan 28;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0
2. Targeted therapy momelotinib provides significant symptom and anemia improvements in patients with myelofibrosis. News Release. MD Anderson. January 27, 2023. Accessed January 31, 2023. https://bit.ly/3RtjQDi
3. US FDA accepts new drug application for GSK’s momelotinib for the treatment of myelofibrosis. News release. GSK. August 17, 2022. Accessed January 31, 2023. https://bit.ly/3Hm7rME