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Momelotinib provided a statistically significant benefit in terms of splenic symptoms, anemia, and splenic size in patients with myelofibrosis.
Momelotinib provided a statistically significant benefit in terms of splenic symptoms, anemia, and splenic size in patients with myelofibrosis, meeting all prespecified primary and key secondary end points of the phase 3 MOMENTUM trial (NCT04173494).1
Topline data demonstrated that 25% of patients who received momelotinib (n = 130) had a total symptom score (TSS) of 50% or higher vs 9% of those who were given danazol (n = 65; P = .0095). Moreover, 31% of those in the investigative arm achieved transfusion independence (TI) vs 20% of those in the control arm (1-sided P = .0064; non-inferiority). Twenty-three percent of patients who received momelotinib experienced a splenic response rate (SRR) of at least 35% vs 2% of those given danazol (P = .0006).
Regarding safety, 54% of patients in the momelotinib arm experienced grade 3 or higher toxicities in the randomized treatment period vs 65% of those on the danazol arm. Serious treatment-emergent adverse effects were experienced by 35% and 40% of those in the investigative and control arms, respectively.
The full data set are slated to be shared at an upcoming medical meeting.
“As one of the co-developers of the symptom assessment tools and understanding symptoms for patients with myelofibrosis I was very excited to see that the primary end point, which was improvement in symptoms was vastly superior with momelotinib vs danazol,” Ruben Mesa, MD, FACP, executive director of the Mays Cancer Center, home to UT Health San Antonio, MD Anderson Cancer Center, and co-principal investigator of the study, told OncLive®. “Importantly, TI was noninferior [between the arms], clearly leaning toward momelotinib. The spleen volume reduction was vastly superior for momelotinib vs danazol. This drug is treating symptoms, splenomegaly, anemia—it’s really treating the whole disease.”
A selective, oral JAK1/2 and ACVR1/ALK2 inhibitor, momelotinib has showcased clinical activity against myelofibrosis, which results from dysregulated JAK-STAT signaling. The agent represents a potential therapeutic option for disease-related constitutional symptoms, splenomegaly, and progressive anemia.
“Momelotinib has been in development as therapy for myelofibrosis for a very long period of time,” Srdan Verstovsek, MD, PhD, United Resources, Inc. Professor of Medicine and hematologist/oncologist in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, told OncLive®. “Finally, after initial attempts to develop it as a medication to control just the splenic symptoms, we realized that it could impact anemia in a positive way; it can improve the anemia parameters and make patients achieve TI and this is because it has a dual mode of action.”
The double-blind, global trial enrolled patients with primary myelofibrosis, post–polycythemia vera (PV) myelofibrosis, or post–essential thrombocytopenia (ET) myelofibrosis. To be eligible for enrollment, patients needed to be at least 18 years of age, have symptomatic disease, and anemia.2 Patients must have received prior treatment with an approved JAK inhibitor for their disease for at least 90 days. Moreover, they needed to have baseline splenomegaly, as well as high-risk, intermediate-2 or intermediate-1 risk disease.
If patients previously received momelotinib; an approved JAK inhibitor therapy, active anti-myelofibrosis treatment, or potent CYP3A4 inducers within 1 week before randomization; an investigational agent or an erythropoiesis stimulating agent within 4 weeks before randomization; danazol or splenic irradiation within 3 months before randomization; or current treatment with simvastatin, atorvastatin, lovastatin, or rosuvastatin, they were excluded.
A total of 195 participants were randomized 2:1 to once-daily, oral momelotinib (n = 130) vs twice-daily, oral danazol (n = 65). Placebos to match danazol and momelotinib, respectively, were also administered. Those who were given momelotinib can continue the drug in the open-label, extended treatment period until week 204, translating to a treatment period of approximately 4 years. Those in the danazol arm who are responding to treatment can continue for up to 48 weeks.
Following 24 weeks of treatment, patients who received danazol were permitted to crossover to receive momelotinib. Early crossover to momelotinib was available to those who had confirmed symptomatic splenic progression.
The primary end point of the trial is TSS reduction of 50% or higher over the 28 days immediately before the end of week 24 vs baseline TSS utilizing the Myelofibrosis Symptom Assessment Form. Key secondary end points comprised TI rate for 12 weeks or longer immediately before the end of week 24 with hemoglobin levels of at least 8 g/dL, and SRR based on a splenic volume reduction of at least 35% at week 24.
“The safety [data that we have seen thus far] in this study comparing momelotinib with danazol to me, as a clinical investigator, [were] extraordinary. The percentage of patients who had grade 3 or 4 toxicities were numerically higher on the danazol arm vs the momelotinib arm,” Verstovsek added. “That tells you that this a very safe drug. You can then envision that it can be easily combined with other drugs. [In fact], one of the possible next steps is to combine it with a BET inhibitor; this combination is very attractive.”