Molotinib/mometinib wins Canadian approval for the treatment of myelofibrosis with anemia

Health Canada has approved Momelotinib-Ojjaara for the treatment of splenomegaly and/or disease-related symptoms in adult patients with moderate to severe anemia at moderate or high risk for primary myelofibrosis, post-polycythemia vera or essential thrombocythemia myelofibrosis. This regulatory decision is supported by results from the pivotal Phase 3 global, multicenter, randomized, double-blind MOMENTUM trial (NCT04173494), which compared molotinib (n=130) with danazol (n=65) in patients with anemic, symptomatic myelofibrosis and previous exposure to an approved JAK inhibitor.

Overall, 25% of patients in the molotinib group reported at least a 50% reduction in total symptom score (TSS) compared with 9% in the danazol group (difference in proportions, 16%; 95% CI, 6%-26%; P<0.01). 2 Additionally, between Weeks 12 and 24, 30% of patients treated with molotinib achieved transfusion independence compared with 20% of patients treated with danazol (noninferiority treatment difference, 14%; 95% CI, 2%-25%; P=0.023). Overall, 35% of patients in the molotinib group and 17% of patients in the danazol group, respectively, did not require a transfusion during 24 weeks of treatment (treatment difference, 17%; 95% CI, 8%-26%; P=0.001).

A spleen volume reduction (SVR) of at least 25% was reported in 39% of patients in the molotinib group and 6% in the danazol group, respectively (treatment difference, 33%; 95% CI, 23%-44%; P<0.0001). Among these groups, an SVR of at least 35% (SVR35) was observed in 22% and 3%, respectively (treatment difference, 18%; 95% CI, 10%-27%; P=0.001). In addition, the Myelofibrosis Symptom Assessment Table 4.0 showed that the TSS change from baseline was -9.4 in the molotinib group and -3.1 in the danazol group (treatment difference, -6.2; 95% CI, -10 to -2.4).

Treatment options for anemia associated with myelofibrosis are limited. We are proud to offer this treatment option to Canadian patients to address this critical unmet need and other myelofibrosis symptoms. With the majority of patients with myelofibrosis becoming anemic over time, the approval of molotinib is an important milestone in improving outcomes for these patients and underscores GlaxoSmithKline's commitment to making an impact in the Canadian hematology-oncology field through innovative new therapies.

Additional support for this regulatory decision comes fromData from a subset of patients with moderate to severe anemia at baseline from the phase 3, multicenter, randomized, double-blind SIMPLIFY-1 trial (NCT01969838) comparing molotinib (n=215) and ruxolitinib tablets (ruxo litinib; n=217) in myelofibrosis patients who had not previously received a JAK inhibitor, SVR35 was achieved in 35% (95% CI, 21.8%-42.3%) of patients in the ruxolitinib arm. Of note, the percentage of molotinib-treated patients who reported at least a 50% reduction in TSS score at week 24 was numerically lower than that of ruxolitinib-treated patients, at 25% and 36%, respectively.

Anemia and associated transfusions significantly impact quality of life, prognosis, and survival in patients with anemia [myelofibrosis]. Progress in this rare disease area and seeing [molotinib] approved in Canada. This new therapy has the potential to help improve patients' lives while addressing the main challenges of the disease, namely anemia and other key symptoms.

Reference materials:https://www.onclive.com/view/momelotinib-wins-canadian-approval-for-myelofibrosis-with-anemia