Health Canada has approved momelotinib (Ojjaara) for the treatment of splenomegaly and disease-related symptoms in adult patients with intermediate- or high-risk primary myelofibrosis, post–polycythemia vera or essential thrombocythemia myelofibrosis who have moderate-to-severe anemia. This approval marks a significant advancement in treating myelofibrosis-related anemia, an area with limited therapeutic options.
The regulatory decision was primarily supported by data from the phase 3 MOMENTUM trial, a global, multicenter, randomized, double-blind study. The trial compared momelotinib (n = 130) with danazol (n = 65) in myelofibrosis patients who were anemic, symptomatic, and had prior exposure to a JAK inhibitor. The results demonstrated a statistically significant improvement in total symptom score (TSS) reduction of at least 50% in 25% of patients in the momelotinib arm compared to 9% in the danazol arm (proportion difference, 16%; 95% CI, 6%-26%; P < .01).
Key Findings from MOMENTUM Trial
Momelotinib also showed a higher rate of transfusion independence, with 30% of patients achieving independence between weeks 12 and 24, compared to 20% in the danazol arm (noninferiority treatment difference, 14%; 95% CI, 2%-25%; P = .023). Furthermore, 35% of patients in the momelotinib arm required no transfusions during the 24-week treatment period, versus 17% in the danazol arm (treatment difference, 17%; 95% CI, 8%-26%; P = .001).
Significant spleen volume reduction (SVR) was also observed in the momelotinib arm, with 39% of patients achieving at least a 25% reduction compared to 6% in the danazol arm (treatment difference, 33%; 95% CI, 23%-44%; P < .0001). An SVR of at least 35% was seen in 22% of patients treated with momelotinib, versus 3% in the danazol group (treatment difference, 18%; 95% CI, 10%-27%; P = .001).
Additional Data from SIMPLIFY-1 Trial
Additional support for the approval came from a subset of patients with moderate to severe anemia at baseline in the phase 3 SIMPLIFY-1 trial. This multicenter, randomized, double-blind study compared momelotinib (n = 215) with ruxolitinib (n = 217) in patients with myelofibrosis who had not previously received a JAK inhibitor. The SIMPLIFY-1 trial indicated that 31.4% (95% CI, 21.8%-42.3%) of patients in the momelotinib arm achieved SVR35 compared to 32.6% (95% CI, 23.4%-43.0%) in the ruxolitinib arm. However, the percentage of patients treated with momelotinib who reported a TSS score reduction of at least 50% at week 24 was numerically lower than that of patients treated with ruxolitinib, at 25% vs 36%.
Expert Commentary
Michelle Horn, interim country medical director of GSK Canada, stated, "Treatment options for myelofibrosis-related anemia have been limited. We are proud to offer this treatment alternative for Canadian patients to address this critical unmet need and other myelofibrosis symptoms... With most [patients with] myelofibrosis becoming anemic over time, [momelotinib’s] approval represents a significant milestone to improve the outcomes of these patients while also highlighting GSK’s commitment to making an impact in Canada’s hematology oncology space through innovative new treatments."
Cheryl Petruk, chief executive officer of HEAL Canada, added, "Anemia and related transfusions significantly affect the quality of life, prognosis, and survival for anemic [patients with] myelofibrosis... We are excited to witness progress in this rare disease space and to see [momelotinib] approved in Canada. This new treatment has the potential to help improve the lives of patients while addressing the disease’s main challenges, namely anemia and other major symptoms."
