Momelotinib noninferior to ruxolitinib for spleen response in myelofibrosis
CHICAGO — Spleen response with momelotinib appeared noninferior to that of ruxolitinib among treatment-naive patients with myelofibrosis, according to results from the phase 3 Simplify clinical trial presented at ASCO annual meeting.
Momelotinib (Gilead Sciences) did not meet noninferiority criteria for the key secondary endpoints of symptom response, but demonstrated an association with a reduced transfusion requirement.
Momelotinib — a small molecule inhibitor of JAK1 and JAK2 mutations — exhibited durable spleen and anemia responses in earlier phase 1 and 2 clinical trials.
“Momelotinib has been demonstrated with this anemia benefit to potentially have ... mechanisms of action to impact anemia,” Ruben A. Mesa, MD, deputy director of Mayo Clinic Cancer Center in Arizona and HemOnc Today Editorial Board member, said during his presentation. “In the setting of momelotinib, it could potentially have an impact on the pathway because it inhibits type 1 activin A receptor; receptor leads to increased hepcidin gene expression; hepcidin decreases plasma iron; and hepcidin is elevated in myelofibrosis. This is a specific mechanism of action that has been validated in a rodent model.”
Mesa and colleagues randomly assigned 432 patients to 200 mg momelotinib every day (n = 215; median age, 67 years) or 20 mg ruxolitinib (Jakafi, Incyte; n = 217; median age, 66 years) twice daily for 24 weeks. After completion of therapy at 24 weeks, patients had the option to receive momelotinib for up to an additional 168 weeks.
All patients were treatment-naive to a JAK inhibitor, Mesa noted.
Splenic response rate at 24 weeks — a greater than 35% reduction in splenic volume from baseline — served as the primary endpoint. Secondary endpoints included Total Symptom Score, red blood cell transfusion independence rate and red blood cell transfusion rate at 24 weeks.
A total of 175 patients (81%) treated with momelotinib and 201 patients (93%) treated with ruxolitinib completed 24 weeks of therapy. Forty patients treated with momelotinib (19%) and 16 patients treated with ruxolitinib (7%) discontinued treatment.
Five patients treated with momelotinib died.
The mean total duration of exposure was 21.3 weeks (standard deviation [SD] = 6.37) for momelotinib-treated patients and 23.3 weeks (SD = 3.13) for ruxolitinib-treated patients.
Patients achieved a splenic response rate of 26.5% with momelotinib and 29% with ruxolitinib, indicating that momelotinib was noninferior to ruxolitinib, Mesa said.
Researchers reported a 24-week transfusion independence rate of 66.5% in patients treated with momelotinib compared with 49.3% in patients treated with ruxolitinib (P < .001).
Patients demonstrated a transfusion dependence rate of 30.2% with momelotinib compared with 40.1% with ruxolitinib, indicating momelotinib failed to meet noninferiority criteria for the key secondary endpoints of symptom response.
The most common grade 3 or worse adverse events among patients treated with momelotinib included thrombocytopenia (7%) and anemia (6%). Among patients treated with ruxolitinib, the most common events included anemia (23%), thrombocytopenia (5%) and neutropenia (5%).
Seven percent of patients in the momelotinib group had grade 3 or worse infections compared with 3% of patients in the ruxolitinib group.
“Patients treated with momelotinib had improved anemia and transfusion requirements compared with patients treated with ruxolitinib,” Mesa said. – by Melinda Stevens
Mesa RA, et al. Abstract 7000. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: Mesa reports honoraria from AOP Orphan Pharmaceuticals, Novartis and Shire; consultant/advisory roles with Baxalta, Galena Biopharma, Incyte and Novartis; research funding to his institution from Celgene, CTI, Genentech, Gilead Sciences, Incyte, NS Pharma, Pfizer, Pharmaessentia and Promedior; and travel, accommodations and expenses from AOP Orphan Pharmaceuticals, Incyte and Novartis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.