Momelotinib Demonstrates Improved Spleen and Symptom Requirements Among Subgroup of Patients With JAK Inhibitor-Naive Myelofibrosis

Efficacy/Safety Analysis Results from the Phase 3 SIMPLIFY-1 Study

According to an efficacy/safety analysis of a subgroup of the phase 3, randomized SIMPLIFY-1 trial comparing ruxolotinib with momelotinib, momelotinib was found to be well-tolerated, improved spleen and symptom responses, and reduced transfusion requirements among Japanese patients with Janus kinase (JAK) inhibitor-naïve myelofibrosis.

“Momelotinib has been assessed in 3 randomized phase 3 studies (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2) and demonstrated improvements in symptoms, spleen size and anemia in patients with MF,” stated first study author Kazuya Shimoda, MD, PhD, University of Miyazaki, Miyazaki, Japan, and colleagues.

To confirm that momelotinib is a safe, efficacious, and applicable treatment to diverse patient populations, researchers conducted a Japanese subgroup analysis of the SIMPLIFY-1 study. Eligible patients included those aged ≥ 18 years old with palpable splenomegaly ≥ 5 cm below the left costal margin and a confirmed diagnosis of primary MF (PMF) or post- polycythemia vera (PV)/essential thrombocythemia myelofibrosis (ET MF) in accordance with the World Health Organization (for PMF) or International Working Group for Myelofibrosis Research and Treatment criteria (for post-PV/ET MF).

This analysis included 15 Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9), and it was noted all patients completed treatment. The primary end point was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks, and the main secondary end points were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Patients were randomized on a 1-to-1 basis to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks. Following this, patients could receive open label momelotinib.

Results demonstrated at week 24, SRR was measured at 50% with momelotinib and 44.4% with ruxolitinib. Furthermore, TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%, respectively. Safety measurements determined any-grade treatment-related adverse event rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 treatment-related adverse event rates were 0% and 55.6%, specifically anemia (55.6%) and vertigo (11.1%) with ruxolitinib. 

“Overall, momelotinib was well-tolerated and had an acceptable safety profile in Japanese patients,” concluded Dr Shimoda and coauthors.

Source:

Shimoda K, Komatsu N, Matsumura I, et al. Momelotinib versus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: an efficacy/safety analysis in the Japanese subgroup of the phase 3 randomized SIMPLIFY-1 trial. Int Journ of Hem. Published online August 7, 2024. doi: 10.1007/s12185-024-03822-z