Momelotinib Approaches EU Approval for Myelofibrosis With Anemia

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion supporting the approval of momelotinib for the treatment of disease-related splenomegaly or symptoms in adult patients with moderate to severe anemia with primary myelofibrosis, post–polycythemia vera (PV) myelofibrosis, or post–essential thrombocytopenia (ET) myelofibrosis who have not been exposed to a JAK inhibitor or who had received prior ruxolitinib (Rituxan).¹

The recommendation is supported by findings from the phase 3 MOMENTUM trial (NCT04173494) and a subset of patients with moderate to severe anemia from the phase 3 SIMPLIFY-1 trial (NCT01969838).²

Key efficacy data from MOMENTUM showed that 25% of those in the momelotinib arm (n = 130) achieved a Myelofibrosis Symptom Assessment Form (MFSAF v4.0) tumor symptom score (TSS) reduction of 50% or more vs 9% of those in the danazol arm (n = 65), translating to a treatment difference of 16% (95% CI, 6%-26%; P < .01).^2,3 Thirty percent of patients who were given momelotinib achieved transfusion independent (TI) vs 20% of those who were given danazol, which translated to a noninferiority treatment difference of 14% (95% CI, 2%-25%; P = .023).

Moreover, 39% of those in the momelotinib arm experienced a spleen volume response (SVR) of at least 25% vs 6% of those in the danazol arm (difference, 33%; 95% CI, 23%-44%; P < .0001); 22% vs 3% of patients, respectively, achieved a SVR reduction of at least 35% (difference, 18%; 95% CI, 10%-27%; P = .001). The percentage of patients in the momelotinib arm with no transfusions during the 24-week treatment period was 35% vs 17% in the danazol arm (difference, 17%; 95% CI, 8%-26%; P = .001). The MFSAF v4.0 TSS change from baseline with momelotinib was -9.4 vs -3.1 with danazol (difference, -6.2; 95% CI, -10 to -2.4; P = .001).

Findings from SIMPLIFY-1 indicated that 31.4% (95% CI, 21.8%-42.3%) of patients in the momelotinib arm (n = 86) achieved an SVR reduction of at least 35% compared with 32.6% (95% CI, 23.4%-43.0%) of those in the danazol arm (n = 95).

“Momelotinib has a differentiated mechanism of action that may address the significant medical needs of myelofibrosis patients, especially those with moderate to severe anaemia. The vast majority of myelofibrosis patients will develop anaemia, causing them to require transfusions and leading a notable proportion to discontinue treatment,” Nina Mojas, senior vice president of Oncology Global Product Strategy at GlaxoSmithKline, stated in a press release.¹ “This positive CHMP opinion is a significant step in bringing momelotinib to patients in the EU with this difficult-to-treat blood cancer.”

A total of 195 patients with primary myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis who were at least 18 years of age who had prior exposure to a JAK inhibitor for at least 90 days were enrolled in MOMENTUM.^2,3 These patients were symptomatic and had an ECOG performance status of 0 to 2. They were able to have high-risk, intermediate-2 risk, or intermediate-1 risk disease by Dynamic International Prognostic Scoring System criteria.

Patients were randomly assigned in a 2:1 fashion to momelotinib at 200 mg once daily or danazol at 300 mg twice daily for the duration of 24 weeks. Those in the danazol arm switched to open-label treatment with momelotinib. Achievement of an MFSAF v4.0 TSS reduction of at least 50% at week 24 vs baseline represented the primary end point of the trial. Other end points included TI, SVR, MFSAF v4.0 TSS change from baseline, and the percentage of patients without transfusions.

The median patient age was 71 years (range, 38-86); more than half of patients (79%) were aged 65 years and older. More than half of the patients were male (63%), and 81% were White. Sixty-four percent of patients had primary myelofibrosis, 19% had post–PV myelofibrosis and 17% had post–ET myelofibrosis. With regard to risk, 5% had intermediate-1 risk disease, 57% had intermediate-2 risk disease, and 35% had high-risk disease. In the 8 weeks prior to study treatment, 79% of patients had received red blood cell (RBC) transfusions, with a median of 4 RBC units (interquartile range, 1-6).

Thirteen percent of patients in the momelotinib arm were TI at baseline vs 15% of those in the danazol arm. The median hemoglobin count at baseline was 8 g/dL, and the median platelet count was 96 × 10⁹/L (range, 24-733). The median baseline palpable spleen length was 11 cm below the left costal margin, and the median central spleen volume measured by MRI or CT was 2105 cm³ (range, 609-9717).

Regarding safety, the most common adverse effects (AEs) reported in at least 5% of patients who received momelotinib were thrombocytopenia (all grade, 28%; grade ≥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%).

A total of 432 patients had myelofibrosis without previous exposure to a JAK inhibitor were enrolled in SIMPLIFY-1. These patients received the agent at 200 mg at a once-daily dose or ruxolitinib at an adjusted dose twice daily for 24 weeks. Those in the ruxolitinib arm were subsequently able to switch over to receive momelotinib.

In the subset of patients with anemia at baseline (n = 181), the median age was 68 years (range, 25-86), and more than half were 65 years (67%) and male (59%). Eighty-one percent of patients were White. Moreover, 63%, 13%, and 24% of patients had primary myelofibrosis, post-PV myelofibrosis, and post-ET myelofibrosis, respectively. Four percent of patients had intermediate-1 risk disease, 25% had intermediate-2 risk disease, and 71% had high-risk disease. More patients in the ruxolitinib arm were TI at baseline than those in the momelotinib arm, at 44% and 29%, respectively.

An SVR reduction of at least 35% served as the trial’s primary end point.

In terms of safety, the most common AEs experienced by 20% or more of patients 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%).

In September 2023, the FDA approved momelotinib (Ojjaara) for the treatment of adult patients with intermediate- or high-risk myelofibrosis, including primary or secondary myelofibrosis, and anemia.⁴ The decision was based on MOMENTUM data.

A decision on the marketing authorization is expected by early 2024.¹ If approved in the European Union, momelotinib will have the trade name Omjjara.

References

1. GSK receives positive CHMP opinion recommending momelotinib for myelofibrosis patients with anemia. News release. GlaxoSmithKline. November 13, 2023. Accessed November 13, 2023. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-positive-chmp-opinion-recommending-momelotinib-for-myelofibrosis-patients-with-anaemia/
2. Momelotinib (Ojjaara) Prescribing information. GlaxoSmithKline; 2023. Accessed November 13, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF 
3. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0
4. 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 November 13, 2023. 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