New Drug Application Submitted to FDA for Momelotinib in Myelofibrosis

The highly selective JAK inhibitor momelotinib is being considered for the treatment of patients with myelofibrosis by the FDA following submission of a new drug application for this indication.

A new drug application for momelotinib was submitted to the FDA for the treatment of patients with myelofibrosis, according to a press release from developer Sierra Oncology.1

The agent was assessed as part of the phase 3 MOMENTEUM trial (NCT04173494) compared with danazol in patients with myelofibrosis previously treated with a Janus kinase inhibitor (JAK) who were symptomatic and anemic. Findings from the trial, which were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that the primary end point of rate of reduction in total symptom score at or greater than 50% in the momelotinib arm was 25% compared with 9% in the danazol arm (P = .0095).2

Moreover, investigators reported a transfusion independence rate of 31% in the experimental arm compared with 20% in the control arm (1-sided P = .0064) and a splenic response rate of 35% or more in 23% and 3% of each group, respectively (P = .0006). There was also a splenic response rate of 25% or more in 40% vs 6% of patients, respectively.

“Today is truly momentous for everyone at Sierra Oncology and the patients we serve. This team designed a targeted study to address the highest unmet need and delivered incredible results in the midst of a pandemic. We are thrilled to submit this NDA on behalf of myelofibrosis patients and look forward to working with the FDA over the coming months,” Stephen Dilly, MBBS, PhD, president and chief executive officer of Sierra Oncology, said in a press release. “We are immensely grateful to the patients and investigators who participated in momelotinib trials over the years, making it possible to achieve this milestone.”

Additional findings from the study highlighted a trend toward overall survival improvement in the experimental arm, according to data from week 24 (P = .0719) and overall (P = .3510).

In terms of safety, grade 3 adverse effects (AEs) were reported in 54% of those in the experimental arm compared with 65% of patients in the control arm. Moreover, the rate of serious AEs was 35% and 40% in each arm, respectively. Common nonhematologic AEs included diarrhea, nausea, asthenia, pruritis, and increased blood creatinine.

“Receiving an oral presentation at ASCO for our pivotal phase 3 study data—which demonstrated that momelotinib achieved statistically significant and clinically important efficacy across all prespecified and key secondary end points—is truly a momentous occasion for Sierra Oncology,” Barbara Klencke, MD, chief medical officer at Sierra Oncology, stated.2 “[These data] demonstrate the true potential use of momelotinib as the treatment of choice across a range of myelofibrosis patients who are symptomatic and cytopenic, including those with anemia and thrombocytopenia.”

Momelotinib is a selective oral inhibitor of JAK1/JAK2 and ACVR1/ALK2 and is the first drug in its class to show positive results across key features of myelofibrosis: symptoms, splenic response, and anemia.


  1. Sierra Oncology announces submission of new drug application for momelotinib to US Food & Drug Administration. News release. Sierra Oncology. June 17, 2022. Accessed June 20, 2022.
  2. Momelotinib pivotal phase 3 data receives oral presentation at American Society of Clinical Oncology Annual Meeting. News release. Sierra Oncology. May 26, 2022. Accessed June 20, 2022.