Momelotinib Approved in Europe for Myelofibrosis With Anemia

The European Commission has granted marketing authorization for momelotinib (Omjjara), the first agent approved by the European Commission for the treatment of adult patients with disease-related splenomegaly or symptoms and moderate to severe anemia including those who have primary myelofibrosis, post-polycythemia vera (PV) myelofibrosis, or post–essential thrombocythemia (ET) myelofibrosis and who are JAK inhibitor naive or have been previously treated with ruxolitinib (Jakafi).¹

The authorization of the once-a-day, oral JAK1/JAK2 and ACVR1 inhibitor was based on data from the phase 3 MOMENTUM trial (NCT04173494) and data from a subpopulation of patients with moderate to severe anemia from the phase 3 SIMPLIFY-1 trial (NCT01969838). Notably, in September 2023, the FDA granted approval to the agent based on data from the same clinical studies for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.²

“The challenges of living with myelofibrosis can be burdensome, and symptomatic patients can experience spleen enlargement, fatigue, night sweats and bone pain,” senior vice president of Oncology Global Product Strategy at GSK, Nina Mojas, stated in the press release. “Until now, there have been no options specifically indicated to treat these symptoms in patients who also experience anemia. The authorization of [momelotinib] brings a new treatment option with a differentiated mechanism of action to these patients in the European Union [EU].”

Myelofibrosis affects approximately 1 in 10,000 people in the EU. It is also estimated that 40% of patients have moderate to severe anemia at the time of their diagnosis, emphasizing the need for additional supportive care, including transfusions.¹

In the double-blind, active-controlled MOMENTUM trial, investigators enrolled 195 adult patients with primary myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis, who had received a JAK inhibitor for a minimum of 90 days.^2,3

Symptomatic patients with anemia, splenomegaly, and an ECOG performance status of 0 to 2 were randomly assigned to receive either 200 mg of momelotinib once daily (n = 130) or 300 mg of danazol twice daily for 24 weeks (n = 65). The primary end point of the study was a 50% or more reduction in Myelofibrosis Symptom Assessment Form (MFSAF v4.0) Total Symptom Score (TSS) at week 24 vs baseline.³

Results showed that 25% of patients in the momelotinib group achieved a reduction of 50% or more in MFSAF v4.0 TSS compared with 9% of those in the danazol group, resulting in a treatment difference of 16% (95% CI, 6%-26%; P < .01). Moreover, 30% of patients who were treated with momelotinib attained transfusion independence vs 20% in the danazol group, indicating a noninferiority treatment difference of 14% (95% CI, 2%-25%; P = .023).³

Notably, 39% of those in the momelotinib group experienced a spleen volume response (SVR) of at least 25% vs 6% of those in the danazol group, reflecting a difference of 33% (95% CI, 23%-44%; P < .0001).³

In the SIMPLIFY-1 trial, investigators treated patients with myelofibrosis who did not have prior exposure to JAK inhibitor treatment (n = 432), and eligible patients were treated with momelotinib at a once-daily dose of 200 mg or ruxolitinib at an adjusted dose twice daily for 24 weeks.³

In the group of patients with a hemoglobin score of less than 10 g/dL (n = 181), 63%, 13%, and 24% of patients presented with primary myelofibrosis, post-PV myelofibrosis, and post-ET myelofibrosis, respectively. Notably, more individuals in the ruxolitinib arm were transfusion independent at baseline compared with those in the momelotinib arm, at rates of 44% and 29%, respectively. The primary efficacy end point was a 35% or more reduction in SVR; 31.4% (95% CI, 21.8%-42.3%) of patients treated with momelotinib (n = 86) achieved the desired SVR reduction vs 32.6% (95% CI, 23.4%-43.0%) of those in the danazol group (n = 95).³

Regarding safety in MOMENTUM, the most common toxicities that occurred in patients were thrombocytopenia (all grade, 28%), diarrhea (22%), hemorrhage (22%), fatigue (21%), and nausea (16%). In the SIMPLIFY-1 trial, the most common toxicities were dizziness (24%), fatigue (22%), bacterial infection (21%), hemorrhage (21%), and thrombocytopenia (21%).³

Francesca Palandri, MD, PhD, a medical oncologist at the Bologna University Hospital in Italy, stated, “The EU authorization of [momelotinib] represents a meaningful advancement for eligible patients with myelofibrosis, and particularly for those with moderate to severe anemia who need new treatment options that may reduce their disease-related burden. The availability of a single therapy for key manifestations of myelofibrosis is a clear step forward for eligible patients.”¹

References

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