Momelotinib Shows Durability and Safety in Myelofibrosis at 48 Weeks

Aaron T. Gerds, MD, MS, assistant professor in Medicine (Hematology and Medical Oncology) at the Cleveland Clinic, discusses the 48-week results of the MOMENTUM trial (NCT04173494) of momelotinib, a JAK1/JAK2 inhibitor that is being investigated specifically for the treatment of anemic patients with myelofibrosis.

The phase 3 trial randomly assigned patients with myelofibrosis who had received a prior JAK inhibitor and were anemic to receive momelotinib or danazol. Momelotinib is a JAK inhibitor that also inhibits ACVR1, potentially improving anemia, according to Gerds. The primary end points were outcomes at 24 weeks, at which point momelotinib was previously shown to improve anemia in addition to reducing spleen size and symptoms.

Gerds says that after 24 weeks was an open-label period where patients could cross over to receive momelotinib. In the momelotinib arm, 93 out of 130 patients continued in the open-label period, and 41 out of 65 who initially received danazol crossed over. Investigators saw no new safety signals in this period, which is important according to Gerds since patients will likely be on momelotinib for a longer period of time if this agent is used commercially. Additionally, the longer follow-up showed the response to momelotinib to be durable; only a small number of patients in the momelotinib arm lost symptom response or transfusion independence, and none had an increase in spleen size from baseline.

TRANSCRIPTION:

0:08 | MOMENTUM is a phase 3 randomized trial pitting momelotinib versus danazol in patients with myelofibrosis. This study selected patients who had previous JAK inhibitor exposure, were anemic and also significantly symptomatic, and had enlarged spleens. It was looking to see if momelotinib was a better option for these patients. Danazol was chosen as a comparator because it is an active agent in remedying anemia in these folks. Momelotinib is a special JAK inhibitor that not only can shrink spleens and improve symptom burden, but it can also have a potential effect on anemia through inhibition of ACVR1. The week 24 primary end points were already reported at a prior Congress, and this was the updated results for week 48. At week 24, patients were allowed to cross over to open-label momelotinib, even if they were on the momelotinib arm or the danazol arm. So [it was] basically an open-label extension at this point, but we get to continue data.

1:04 | I think the first key take home point from the data we presented was that there were no new toxicity or safety signal seen. The data was very consistent with what we saw in the original 24-week analyses. This is of course incredibly important when you think about the fact that these folks might be on this medication for a long time. Moreover, the responses were quite durable; patients who responded at week 24 continue to respond through week 48, whether we're talking about transfusion independence, spleen volume response or symptom burden and improvement.