Momelotinib Wins Japanese Approval for Myelofibrosis

The Ministry of Health, Labour, and Welfare in Japan has approved momelotinib (Omjjara) for use in patients with myelofibrosis, according to an announcement from GlaxoSmithKline.¹

The regulatory decision is supported by data from the phase 3 MOMENTUM (NCT04173494) and SIMPLIFY-1 (NCT01969838) trials.

In MOMENTUM, 25% of patients who received momelotinib (n = 130) experienced a Myelofibrosis Symptom Assessment Form (MFSAF v4.0) tumor symptom score (TSS) reduction of 50% or higher at week 24 vs baseline compared with 9% of those who were given danazol; this translated to a difference of 16% between the arms, meeting the primary end point of the study (95% CI, 6%-26%; P < .01).² Additionally, 22% of patients in the momelotinib arm experienced a spleen volume response (SVR) reduction of 35% or more vs 3% of those in the danazol arm, translating to a difference of 18% between the arms (95% CI, 10%-27%; P = .001). Lastly, 30% vs 20% of patients in the momelotinib and danazol arms, respectively, achieved transfusion independence (TI), which translated to a noninferiority treatment difference of 14% (95% CI, 2%-25%; P = .023). In SIMPLIFY-1, momelotinib (n = 215) proved noninferior to ruxolitinib (Jakafi; n = 217) with regard to achievement of a SVR reduction of 35% or higher, with a 9% difference between the arms (95% CI, 2%-16%).1 Treatment with momelotinib also resulted in an improved TI rate vs ruxolitinib, at 66.5% and 49.3%, respectively, translating to a difference of 18% between the arms (95% CI, 9%-26%).

“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,” Nina Mojas, senior vice president of Oncology Global Product Strategy at GlaxoSmithKline, stated in a news release. “With the approval of Omjjara, myelofibrosis patients in Japan will have a new treatment option for this complex blood cancer.”

Taking a Closer Look at the MOMENTUM Trial

A total of 195 patients with primary myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocytopenia myelofibrosis were enrolled to the double-blind, active-controlled, phase 3 study. To participate, they needed to be at least 18 years of age, have prior exposure to an approved JAK inhibitor for at least 90 days, an ECOG performance status ranging from 0 to 2, and have symptomatic disease that was defined as a TSS of at least 10 at screening. Patients also needed to be anemia, with a hemoglobin level under 10 g/dL, a platelet count higher than 25 x 10⁹ cells/L and baseline splenomegaly. Patients could have high-risk, intermediate-2 risk, or intermediate-1 risk disease per Dynamic International Prognostic Scoring System criteria.

They were randomized in a 2:1 fashion to once-daily momelotinib at 200 mg or twice-daily danazol at 300 mg for 24 weeks. Those in the danazol arm subsequently switched to open-label treatment with momelotinib. In addition to achievement of a MFSAF v4.0 TSS reduction of at least 50% at week 24 vs baseline serving as the trial’s primary end point, other key end points comprised TI, SVR, MFSAF v4.0 TSS change from baseline, and percentage of patients with no transfusions.

The median patient age was 71 years (range, 38-86), and the majority were male (63%) and White (81%). With regard to disease, most patients had primary myelofibrosis (64%) and intermediate-2 risk disease (57%). In the 8 weeks prior to study treatment, 79% of patients received red blood cell (RBC) transfusions, with a median of 4 RBC units (interquartile range, 1-6). At baseline, 13% of those in the momelotinib arm were TI vs 15% of those in the danazol arm. Median hemoglobin and platelet count at baseline were 8 g/dL and 96 x 10⁹/L, respectively.

Additional efficacy findings showed that a SVR of 25% or higher was achieved by 39% of those in the momelotinib arm vs 6% of those in the danazol arm, translating to a treatment difference of 33% between the arms (95% CI, 23%-44%; P < .0001). Moreover, 35% vs 17% of patients had no transfusions during the 24-week treatment period (difference, 17%; 95% CI, 8%-26%; P = .001). The MFSAF v4.0 TSS change from baseline with momelotinib and danazol were -9.4 and -3.1, respectively, which translated to a difference of -6.2 (95% CI, -10 to -2.4; P = .001).

Regarding safety, the most common adverse effects (AEs) experienced by at least 5% of patients given momelotinib included thrombocytopenia (all grade, 28%; ≥3, 22%), diarrhea (22%; 0%), hemorrhage (22%; 2%), fatigue (21%; 2%), fatigue (21%; 2%), nausea (16%; 2%), bacterial infection (15%; 8%), abdominal pain (13%; 1%), viral infection (12%; 5%), pruritus (11%; 2%), elevated liver enzymes (10%; 2%), pyrexia (10%; 2%), cough (8%; 0%), paresthesia (8%; 1%), dizziness (8%; 2%), and vomiting (8%; 1%).

Taking Stock of the SIMPLIFY-1 Study

The double-blind, active-controlled, phase 3 study enrolled a total of 432 patients with myelofibrosis who had not previously received a JAK inhibitor. They received once-daily momelotinib at 200 mg or twice-daily ruxolitinib at an adjusted dose for 24 weeks. Those in the ruxolitinib arm were permitted to switch over to receive open-label momelotinib.

There was a subgroup of patients who had anemia at baseline; this was defined as having a hemoglobin level under 10 g/dL (n = 181). The median patient age in this subset was 68 years (range, 25-86). Slightly more than half of patients were male (59%) and most were White (81%). Sixty-three percent had primary myelofibrosis and 71% had high-risk disease. More patients in the ruxolitinib arm were TI at baseline vs those in the momelotinib arm, at 44% and 29%, respectively.

The most common AEs observed in at least 20% of the anemic subset included dizziness (any grade, 24%; grade ≥3, 1%), fatigue (22%; 0%), bacterial infection (21%; 8%), hemorrhage (21%; 1%), thrombocytopenia (21%; 11%), diarrhea (20%; 1%), nausea (20%; 0%), abdominal pain (18%; 1%), cough (14%; 0%), hypotension (14%; 2%), pain in extremity (12%; 0%), pyrexia (12%; 1%), rash (12%; 0%), renal and urinary tract infection (12%; 1%), elevated liver enzymes (11%; 4%), headache (11%; 0%), peripheral edema (11%; 0%), arrhythmia (8%; 2%), paresthesia (8%; 0%), pneumonia (8%; 8%), vomiting (8%; 0%), back pain (7%; 1%), viral infection (6%; 0%), and vitamin B1 deficiency (6%; 0%).

Other Indications

In September 2023, the FDA approved momelotinib (Ojjaara) for use in adult patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia, based on data from MOMENTUM and a subpopulation of adult patients with anemia enrolled to SIMPLIFY-1.³ In January 2024, the European Commission granted marketing authorization to momelotinib for adult patients with disease-related splenomegaly or symptoms and moderate-to-severe anemia, including those with primary myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis with no prior exposure to JAK inhibition and who previously received ruxolitinib. This decision was based on MOMENTUM findings and a subpopulation of patients with moderate-to-severe anemia from SIMPLIFY-1.⁴ The agent is also approved in the United Kingdom to treat symptoms experienced by adult patients with myelofibrosis who have moderate-to-severe anemia.

References

1. GSK’s Omjjara (momelotinib) approved in Japan for treatment of myelofibrosis. News release. GlaxoSmithKline, plc. June 24, 2024. Accessed June 24, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-s-omjjara-momelotinib-approved-in-japan-for-treatment-of-myelofibrosis/
2. Momelotinib (Ojjaara) Prescribing information. GlaxoSmithKline; 2023. Accessed June 24, 2024. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF
3. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed June 24, 2024. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia
4. European Commission authorises GSK’s Omjjara (momelotinib). News release. GlaxoSmithKline. January 29, 2024. Accessed June 24, 2024. https://www.gsk.com/en-gb/media/press-releases/european-commission-authorises-gsk-s-omjjara-momelot