FDA Approves Momelotinib for the Treatment of Myelofibrosis and Anemia

• Approval for myelofibrosis and anemia marks the first ever inducation for momelotinib in any market.¹

• The approval comes 4 months after the Prescription Drug User Fee target action date of June 16, 2023.

Approval has been granted by the FDA to momelotinib for the treatment of patients with myelofibrosis and anemia.¹

Results from key phase 3 MOMENTUM trial (NCT04173494) of momelotinib support this FDA approval. The international, randomized, double-blind, controlled, phase 3 study met all of its primary and secondary end points.

“With momelotinib we have the potential to establish a new standard of care for myelofibrosis patients with anemia. Addressing key manifestations of myelofibrosis, including anemia, constitutional symptoms and splenomegaly, makes a significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease,” said Ruben A. Mesa, MD, FACP, president and executive director, Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, in a press release.

MOMENTUM enrolled 307 patients with symptomatic myelofibrosis and anemia, and 195 of those patients were randomized in the study. All patients were 18 years of age or older with a confirmed diagnosis of myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia. Randomization was 2:1, and in the experimental arm, patients were administered oral momelotinib 200 mg, once daily, vs an oral danazol placebo 300 mg, twice daily, or danazol plus placebo, in the comparator arm.²

The primary end point of the study was Myelofibrosis Symptom Assessment Form total symptom score (TSS) response rate at week 24. The secondary end points were the number of patients with transfusion independence, splenic response rate of 25% of greater, absolute TSS change from baseline, splenic response rate of 35% or greater, and rate of zero transfusions to week 24.

At baseline, the study population had a median age of 71 years (range, 67-75 years) in the momelotinib arm and 72 years (range, 67-78 years) in the danazol arm. The patient population was largely male and included 61% of the momelotinib arm and 68% of the danazol arm. The patient population was predominantly White, although 9% in each arm were Asian.

The most common myelofibrosis subtype observed among the study subjects was primary, including 60% of the momelotinib arm and 71% of the danazol arm. Most patients were intermediate-2 stage of high stage and were positive for JAK Val617Phe mutation. ECOG performance status at baseline ranged from 0-2, with most patients showing a score of 1. The median TSS was 26.4% in the momelotinib group and 23.6% in the danazol group. Moreover, patients in both arms had adequate hematologic and organ function at baseline.

Results showed that the TSS response rate was 35% with momelotinib vs only 9% with danazol, resulting in a superiority finding (P = .0095). Momelotinib was found to be non-inferior to danazol in terms of transfusion independence. The transfusion independence rate was 32% in the momelotinib arm compared with 20% in the danazol arm. Regarding splenic response rate of at least 25%, the rate was 40% with momelotinib vs 6% with danazol, a superiority finding (P < .0001).

The absolute TSS change from baseline was superior in the momelotinib arm at –11.5 compared with –3.9 in the danazol arm (P = .0014). In terms of splenic response rate (≥35% reduction), momelotinib also demonstrated superiority. Specifically, 23% of patients in the momelotinib arm had a splenic response rate of 35% or more compared with only 3% of the danazol arm (P = .0006). The rate of zero transfusion at week 24 was 35% in the momelotinib arm compared with 17% in the danazol arm (P = .0002), demonstrating superiority for momelotinib.

The safety profile of momelotinib in the study was consistent with that shown in completed clinical studies. The most common any-grade adverse events in the momelotinib arm vs the danazol arm were diarrhea (22% v 9%), nausea (16% v 9%, asthenia (13% v 9%), and pruritus (11% v 11%). These common AEs appeared to be grade 3 or higher more frequently in the danazol arm compared with the momelotinib arm. The hematologic AEs that occurred during the study in the momelotinib arm vs the danazol arm were anemia (99% v 100%), thrombocytopenia (76% v 62%), and neutropenia (29% v 26%).

"The vast majority of myelofibrosis patients eventually develop anaemia, causing them to discontinue treatments and require transfusions. Given this high unmet need, we are proud to add Ojjaara to our oncology portfolio and address a significant medical need in the community. We look forward to helping improve outcomes in this difficult-to-treat blood cancer, said Nina Mojas, senior vice president, Oncology Global Product Strategy, GSK, in the press release.¹

_REFERENCES:

_{1. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anemia. News release. GSK plc. September 15, 2023. Accessed September 15, 2023. https://tinyurl.com/46h4rrrj}

_{2. Verstovsek S, Gerds AT, Vannucchi 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.}