Will Momelotinib Phase 3 Study Show TSS Reduction in Patients With Myelofibrosis?

As the topline analysis of the phase 3 MOMENTUM study of momelotinib versus danazol in patients with myelofibrosis continues, Sierra Oncology, Inc., announced plans to submit a new drug application to the FDA given the results are positive, according to a press release.¹

Momelotinib, a novel JAK1, JAK2, and ACVR1 / ALK2 inhibitor, was previously investigated in the phase 3 trials SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) has been said to have potential to address an unmet medical need for more treatment options for patients with myelofibrosis. Compared with both ruxolitinib (Jakafi) and best available therapy, investigators saw a 17% increase of patients who were JAK inhibitor-naïve and a 2-fold increase of previously treated patients who achieved or maintained transfusion independence momelotinib.²

MOMENTUM (NCT04173494), a randomized, double-blind, phase 3 study may confirm the efficacy and safety of momelotinib in patients with myelofibrosis.³

"We are really excited at the prospect of seeing topline results from the MOMENTUM study earlier than predicted. This is enabled by the excellent work of the team who have worked extremely hard over recent weeks to ensure quality and completeness of the study data," said Stephen Dilly, MBBS, PhD, president and chief executive officer at Sierra Oncology, in a press release.¹

A total of 195 patients with myelofibrosis will be evaluated in MOMENTUM. Patients are randomized 2:1 to either an arm of oral momelotinib tablets that are self-administered once daily or oral danazol capsules that are self-administered twice daily. The primary end point of the study is total symptom score (TSS) response rate at week 24. The study is also investigating secondary outcomes including transfusion independence status at week 24, and splenic response rate at week 24.²

Patients are eligible to enroll if they are18 years of age or older with a confirmed post-polycythemia vera (PV) myelofibrosis or post-essential thrombocythemia (ET) myelofibrosis, and patients must either be symptomatic or anemic. Patients are also required to have undergone treatment with at least 1 JAK inhibitor for either form of myelofibrosis, be intermediate-1 to high-risk and have acceptable laboratory assessments. These patients could not have an allogeneic stem cell transplant planned.³

The study excluded individuals who were previously treated with momelotinib at any time or a with JAK inhibitor within 2 weeks prior to the trial start date. Patients with active anti-MF therapy within 2 weeks prior to starting the study, potent cytochrome P450 3A4 within 1 week of the trail start date, an investigational agent within 4 weeks, an erythropoiesis-stimulating agent within 4 weeks, danazol within 3 months, splenic irradiation within months or current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin are also excluded. Further, patients who have a history of prostate cancer unless localized or a prostate-specific antigen > 4 ng/mL or unsuitable for spleen volume measurements are also excluded from the study along with patients who have certain comorbidities.

"We look forward to sharing topline results in the next few weeks, and if those data are positive, we are committed to delivering this potential medicine for myelofibrosis patients, particularly those with anemia, as expeditiously as possible,” said Dilly, in the press release.¹

_References:

_{1. Sierra Oncology updates topline data timing for pivotal phase 3 trial of momelotinib in myelofibrosis. News release. January 18, 2022. Accessed January 20, 2022. https://bit.ly/3IqjVSy}

_{2. Chifotides HT, Brose P, Verstovsek S, et al. Momelotinib: an emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol. 2022 Jan 19;15(1):7. doi: 10.1186/s13045-021-01157-4.}

_{3. A study of momelotinib versus danazol in symptomatic and anemic myelofibrosis patients (MOMENTUM). Clinicaltrials.gov. Accessed January 20, 2022.}