Momelotinib Reduces Symptoms and Anemia in Myelofibrosis

Momelotinib, a Janus kinase (JAK) inhibitor, demonstrated benefit by reducing symptoms and anemia in patients with myelofibrosis in the phase 3 MOMENTUM trial (NCT04173494), according to a press release from Sierra Oncology.¹

The purpose of this trial was to determine the safety and efficacy of momelotinib. It met its primary end point, with 25% of patients who received it having a total symptom score (TSS) of 50% or more, significantly higher than the control arm. The topline data also showed that all secondary end points were met.

“These data are extremely exciting and everything we had hoped to see from the trial,” Stephen Dilly, MBBS, PhD, president and chief executive officer of Sierra Oncology, said in a statement. “To achieve statistically significant and clinically important efficacy across all prespecified primary and key secondary end points while maintaining platelet counts in such a difficult to treat patient population is remarkable, and a confirmation of the anemia response we identified in the comprehensive review of our previous phase 3 studies.”

The MOMENTUM trial was meant to evaluate the benefits of momelotinib versus danazol in reducing disease-related symptoms, especially anemia requiring blood transfusions and enlarged spleen, in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Patients must have been symptomatic and anemic as well as having received a JAK inhibitor.

Patients were randomized 2:1 to momelotinib plus placebo or danazol plus placebo. twice daily. They were evaluated for symptoms in the 28 days prior to week 24 of treatment, and following this period, patients in the control arm could cross over to the momelotinib arm. In addition to the primary end point of TSS, secondary end points were transfusion independence (TI) and splenic response rate (SRR) at week 24.

The percentage of patients in the momelotinib arm with a TSS of 50% or more was 25% compared with only 9% in the control arm (P = .0095). In the momelotinib arm, 31% had a TI status, indicating they had not required red blood cell transfusion in 12 weeks, versus 20% in the control arm (1-sided P = .0064; non-inferiority). Twenty-three percent of patients in the momelotinib arm had a SRR of 35% or more versus only 3% in the control arm (P = .0006).

Currently approved JAK inhibitors for myelofibrosis such as ruxolitinib (Jakafi) and fedratinib (Inrebic) are myelosuppressive and do not address anemia. Danazol is currently approved for treatment of anemia in patients with myelofibrosis and recommended by National Comprehensive Cancer Network guidelines in certain circumstances.²

“Anemia of myelofibrosis is strongly correlated with reduced quality of life and a decrease in overall survival,” said Ruben Mesa, MD, director of the Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, and co-principal investigator of the study.¹ “Half of all [patients with] myelofibrosis present with anemia at diagnosis and virtually all become anemic over time. With currently approved therapies being myelosuppressive, it’s wonderful to know that we may soon have such an effective treatment option for these patients.”

The rate of grade 3 or higher adverse events (AEs) during the randomized period of the trial was 54% in the momelotinib arm versus 65% in the control arm. The serious treatment-emergent AE rate was 35% in the momelotinib arm compared with 40% in the control arm.

“We are committed to working tirelessly to bring momelotinib to patients as quickly as possible,” said Barbara Klencke, MD, chief medical officer of Sierra Oncology, in a press release. “We would like to thank the patients and investigators who participated in this study and look forward to presenting the full data set at an upcoming medical meeting.”

_References:

_{1. Sierra Oncology announces momelotinib achieved statistically significant benefit on symptoms, anemia and splenic size in the pivotal MOMENTUM study for myelofibrosis. Sierra Oncology. Published January 25, 2022. Accessed February 1, 2022. https://bit.ly/3rj45TZ}

_{2. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 2.2021. Accessed February 1, 2022. https://bit.ly/3riyOjM}