Momelotinib Demonstrates Efficacy, Safety vs Ruxolitinib for Myelofibrosis in Japanese Subpopulation Analysis

Momelotinib (Ojjaara; GSK) demonstrated favorable tolerability and spleen volume reduction (SVR) compared with ruxolitinib (Jakafi; Incyte Corp) in Janus kinase (JAK) inhibitor–naïve patients with myelofibrosis, according to a subanalysis in a small group of Japanese patients. The data come out of the main phase 3 SIMPLIFY-1 trial (NCT01969838) to determine the efficacy and safety of momelotinib for treatment of primary myelofibrosis (PMF), post-polycythemia vera or post-essential thrombocythemia myelofibrosis.¹

The data suggests that momelotinib may be an efficacious alternative therapy for patients with MF who discontinue use of ruxolitinib. Image Credit: © Jasmine - stock.adobe.com

Myelofibrosis is a rare myeloproliferative neoplasm characterized by fibrosis, or scarring, of the bone marrow caused by reduced blood cell reduction. JAK inhibitors are the recommended treatment for patients with myelofibrosis, offering durable and tolerable symptom relief. Momelotinib is ATP-competitive small molecule inhibitor of JAK proteins that was approved by the FDA on September 15, 2023, for use in anemic patients with high/intermediate risk MF.^2,3

In the phase 3, randomized, double-blind, active-controlled study, researchers evaluated the safety and efficacy of momelotinib versus ruxolitinib in the Japanese subgroup of the analysis. In the subanalysis, 15 Japanese patients across 9 study centers in Japan were assigned in a 1:1 randomized fashion to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily for 24 weeks. At the end of the treatment period, patients from both cohorts were given the opportunity to receive momelotinib for up to an additional 216 weeks during the open-label phase or discontinue treatment.⁴

The primary end point was an SVR of ≥ 35% reduction (SVR35), which was measured at baseline, week 12, and week 24 during the double-blind phase and every 12 weeks from week 36 during the open-label phase. The trial included a secondary end point of total symptom score at week 24, as defined by the proportion of patients who achieved ≥ 50% reduction in TSS from baseline.⁴

In the double-blind phase, 50% of patients who received momelotinib achieved SVR35 at week 24 compared with 44% from the ruxolitinib group. The researchers observed a ≥ 50% reduction in TSS in the momelotinib group compared with ruxolitinib (33.3% [2/6] and 0% [0/9], respectively). Additionally, momelotinib was associated with an increased therapeutic index of 50% to 83.3% from baseline to week 24 while ruxolitinib saw a decrease from 88.9% to 44.4%.⁴

In the open-label phase at week 48, all patients were eligible to receive momelotinib and splenic response rate (SRR) was used as the primary indicator of efficacy. Patients treated with momelotinib demonstrated a SRR in 50% compared with 55.6% of patients who switched from to momelotinib from ruxolitinib. The researchers also reported that SRR was maintained from week 24 to 48 in the momelotinib group; however, those in the “switch” group saw an SRR increase from 44.4% to 55.6%.⁴

Both momelotinib and ruxolitinib were associated treatment-emergent adverse events (TEAEs) in 83.3% and 88.9%, respectively. The most common any-grade TEAEs were thrombocytopenia (16.7%), hyperuricemia (16.7%) and peripheral sensory neuropathy (16.7%) in patients who received momelotinib, and anemia (66.7%) and thrombocytopenia (33.3%) in patients who received ruxolitinib. There were no TEAEs in either treatment arm that led to death.⁴

The data supports that momelotinib and ruxolitinib are safe and well tolerated treatments to improve SVR and other MF symptoms. However, momelotinib showed a more clinically meaningful and durable spleen response, symptoms and anemia-related responses, including in patients who crossed over from ruxolitinib. The study requires further investigations due to the researchers’ descriptive approach and small sample size. Yet, the data suggests that momelotinib may be an efficacious alternative therapy for patients with MF who discontinue use of ruxolitinib.

REFERENCES

1. Momelotinib versus ruxolitinib in subjects with myelofibrosis (simplify 1). ClinicalTrials.gov Identifier: NCT01969838. Updated May 12, 2023. Accessed October 17, 2024. https://clinicaltrials.gov/study/NCT01969838

2. Tefferi A, Pardanani A. Momelotinib for myelofibrosis: our 14 years of experience with 100 clinical trial patients and recent fda approval. Blood Cancer J. March 18, 2024. doi:10.1038/s41408-024-01029-3

3. Study demonstrates safety, efficacy of luspatercept for mf-related anemia. Pharmacy Times. September 19, 2024. Accessed October 17, 2024. https://www.pharmacytimes.com/view/study-demonstrates-safety-efficacy-of-luspatercept-for-mf-related-anemia

4. Shimoda K, Komatsu N, Kosugi H, 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 J Hematol. August 7, 2024. doi:10.1007/s12185-024-03822-z