Momelotinib Receives Japanese Approval for Treatment of Myelofibrosis

The approval was based on data from the phase 3 MOMENTUM trial (NCT04173494) and phase 3 SIMPLIFY-1 trial (NCT01969838).

Momelotinib (Omjjara), a once daily oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor, has been approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) in use for patients with myelofibrosis and anemia, according to a news release from the developers, GSK.¹

Approved for use in newly diagnosed and previously treated myelofibrosis, momelotinib may address key manifestations of the disease, including constitutional symptoms, splenomegaly, and anemia. Approximately 70% of Japanese patients with primary myelofibrosis have moderate to severe anemia at diagnosis.

“Myelofibrosis has a heavy disease burden, with symptomatic patients experiencing spleen enlargement, fatigue, night sweats and bone pain, along with [anemia], which can lead to treatment discontinuation and dependence on regular blood transfusions,” said Nina Mojas, senior vice president of Oncology Global Product Strategy.¹ “With the approval of [momelotinib], [patients with] myelofibrosis in Japan will have a new treatment option for this complex blood cancer.”

The approval was based on data from the phase 3 MOMENTUM trial (NCT04173494) and phase 3 SIMPLIFY-1 trial (NCT01969838).

Phase 3 MOMENTUM Trial

The MOMENTUM trial tested momelotinib vs danazol in patients with symptomatic and anemic myelofibrosis previously treated with a JAK inhibitor.² The primary end point was total symptom score (TSS), and secondary end points were percent of patients with transfusion independence (TI), splenic response rate (SRR) reduction at 35% or greater from baseline, change in baseline in TSS, SRR reduction at 25% or greater from baseline, and rate of zero transfusions from baseline.

At the week 24 end point of the trial, TSS response rate were 24.6% vs 9.2% (P = 0.0095) among the momelotinib and danazol arms, respectively. Furthermore, TI rates were 30.8% vs 20.0% (P = 0.0064), SRR reductions at 25% or greater occurred in 40.0% vs 6.2% (P <.0001), TSS changes from baseline were –9.36 vs –3.13 (P = 0.0014), SSR reductions at 35% or greater were 23.1% vs 3.1% (P = 0.0006), and zero transfusion rates were 35.4% vs 16.9% (P = 0.0012) among the momelotinib and danazol arms, respectively.

The most common grade 3 or greater treatment-emergent adverse effects (TEAEs) in the momelotinib and danazol arms, respectively, were thrombocytopenia (22% vs 12%) and anemia (8%, 11%), with grade 3 or greater infections occurring in 15% and 17%. Grade 2 or lower peripheral neuropathy occurred in 4% and 2% of patients in each arm, with no discontinuations among either cohort. TEAEs led to drug discontinuation in 18% of the momelotinib arm and 23% of the danazol arm.

Of 130 patients in the momelotinib arm and 65 patients in the danazol arm, 94 (72%) and 38 (58%) completed a 24-week randomized treatment phase. Median baseline TSS were 28 and 26, hemoglobin (HgB) levels were 8.1 and 7.9 g/dL, platelets were 97 x 10⁹ and 94 x 10⁹/L, and baseline TI rates were 13% and 15% for the momelotinib and danazol arms, respectively. Additionally, a trend toward improved overall survival up to week 24 was seen with momelotinib vs danazol (HR = 0.506; P = 0.0719).

Phase 3 SIMPLIFY-1 Trial

The SIMPLIFY-1 trial tested momelotinib vs ruxolitinib (Jakafi) in patients with symptomatic and anemic myelofibrosis not previously treated with a JAK inhibitor.³ The primary end point was a 35% or greater reduction in spleen volume at 24 weeks of therapy. Secondary end points were rates of symptom response and effects on red blood cell (RBC) transfusion requirements.

At the week 24 end point of the trial, A 35% or greater reduction in spleen volume was observed in 26.5% and 29% of the momelotinib and ruxolitinib arms (P = .011), respectively. Additionally, a 50% or greater reduction in TSS was observed in 28.4% and 42.2% of patients who received momelotinib and ruxolitinib, respectively, with noninferiority not being met (P = 0.98). Furthermore, RBC transfusion rates (momelotinib, 0.0 units per month; ruxolitinib, 0.4 units per month; P <.001), transfusion independence (66.5% vs 49.3%, P <.001), and transfusion dependence (30.2% vs 40.1%, P = .019) improved with momelotinib use.

The most common grade 3 or higher TEAEs were hematologic abnormalities, which included thrombocytopenia and anemia in both arms. Grade 3 or higher infections occurred in 7% and 3% of the momelotinib and ruxolitinib arms, respectively. Additionally, grade 2 or lower TE peripheral neuropathy occurred in 10% of the momelotinib arm, and grade 3 or lower TE peripheral neuropathy occurred in 5% of patients who received ruxolitinib.

Of the 432 patients selected for the trial, 215 were assigned to receive momelotinib, and 217 were assigned to receive ruxolitinib. Of those patients, 175 in the momelotinib arm and 201 in the ruxolitinib arm completed the 24-week double blind phase. In this phase, patients were randomly assigned to 200 mg of momelotinib once daily or 20 mg of ruxolitinib twice daily, with treatment assignment stratified based on transfusion dependence and platelet count.

The FDA approved momelotinib for intermediate- or high-risk myelofibrosis in patients with anemia in September 2023 based on findings from the MOMENTUM trial and the SIMPLIFY-1 trial.⁴

References

1. GSK’s Omjjara (momelotinib) approved in Japan for treatment of myelofibrosis. News release. GSK. June 24, 2024. Accessed June 24, 2024. https://tinyurl.com/7j63pzj4
2. Mesa RA, Gerds AT, Vannucchi A, et al. MPN-478 MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. J Clin Oncol. 2022;40(suppl 16):7002. doi:10.1200/JCO.2022.40.16_suppl.7002
3. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. J Clin Oncol. 2017;34(suppl 34):3844-3850. doi:10.1200/JCO.2017.73.4418
4. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia, News release. GSK. September 15, 2023. Accessed June 24, 2024. https://tinyurl.com/bdz5uu39