Exploring the Benefits of Momelotinib for Patients With Myelofibrosis, Including With Anemia

Findings from the Phase 3 MOMENTUM Trial

Aaron Gerds, MD, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, discussed the findings from the phase 3 MOMENTUM trial, which demonstrated the benefits of momelotinib among patients with myelofibrosis (MF), including those with anemia. These results served as the basis for the approval of momelotinib by the U.S. Food and Drug Administration (FDA). 

Transcript: 

My name is Aaron Gerds, and I'm the lead author of a paper that was published in Lancet Hematology regarding the MOMENTUM Study, a prospective randomized trial with momelotinib versus danazol in patients with myelofibrosis. I'm currently an associate professor of medicine at the Cleveland Clinic Taussig Cancer Institute. 

The MOMENTUM study is an incredibly important step forward for the treatment of patients with myelofibrosis and served as the basis for the new drug application for momelotinib, a drug that was approved in September of 2023 for the treatment of myelofibrosis with concurrent anemia. Momelotinib sets itself apart from other [Janus kinase] (JAK) inhibitors, given the fact that it inhibits [activin A receptor, type 1] (ACVR1) which can lower hepcidin levels making iron available for erythropoiesis, thus, alleviating anemia of inflammatory block. 

MOMENTUM was a prospective randomized trial comparing momelotinib versus danazol in patients with anemia and myelofibrosis who were also symptomatic. The primary analysis was at week 24, and in that analysis, momelotinib was better than danazol at symptom burden improvement [and] spleen volume reduction and was not inferior to danazol in terms of transfusion independence.

Danazol was chosen for that reason because it is an active agent in treating anemia in patients with myelofibrosis. After week 24, patients could continue on blinded therapy. Additionally, patients who were not deriving complete and total benefit, if you will, from their blinded treatment, were allowed to cross over to open-label momelotinib. That was kind of the crux of the article that we published in Lancet Hematology, [it] was that after week 24, patients on momelotinib continued to derive benefits. 

We even saw some late responder patients who did not have transfusion independence in the first 24 weeks, [and] did so in the second 24 weeks. Patients also on momelotinib then had late symptom responses or continued symptom responses. [This is] kind of driving home the point that continued therapy with momelotinib may lead to additional patients deriving benefit. But more importantly, the responses that we're seeing with momelotinib in terms of spleen volume response, symptom burn improvement, and anemia improvements, were continued through week 48.

It wasn't just a flash in the pan at week 24; these responses continue out through extended follow-up. Even more important than that, no new safety signals were seen in patients receiving momelotinib. There was no increase in the number of patients having peripheral neuropathies, [gastrointestinal] (GI) toxicity, or myelosuppression due to the treatment of momelotinib. 

Again, this study served as the basis for the new drug application and subsequent approval of momelotinib here in the United States by the US FDA, which I think is an important step forward for the care of patients with myelofibrosis. More importantly, given the effect on anemia or perhaps even less myelosuppression than other JAK inhibitors, momelotinib positions itself as a good partner for combination therapies for future studies. 

Also, combining agents that have different mechanisms of action to treat anemia would be an important avenue to explore going forward. So taking drugs like erythropoiesis-stimulating agents and combining [them] with momelotinib to see if we can make bigger inroads on anemia for patients with myelofibrosis, because anemia is so common, roughly 40% of patients will be anemic at the time of diagnosis, and virtually every patient will develop anemia at some point along their disease course. So, being such an important and prevalent consequence of myelofibrosis is important that we continue to develop therapies to remedy it.

Source: 

Gerds AT, Verstovsek S, Vannucchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. Lancet Haematol. Published online: September 2023. doi:10.1016/S2352-3026(23)00174-6