Results from Phase III studies SIMPLIFY-1 and SIMPLIFY-2 for momelotinib to treat myelofibrosis.- Gilead Sciences

Gilead Sciences, Inc. announced top-line results from two Phase III clinical trials (SIMPLIFY 1 and 2) evaluating momelotinib, an investigational inhibitor of Janus kinase (JAK) compared to ruxolitinib or best alternative therapy (BAT) in patients with myelofibrosis. The SIMPLIFY-1 study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for splenic response rate at Week 24 (SRR24), defined as the percentage of patients more than experiencing a more than 35 percent reduction in spleen volume (momelotinib: 26.5%; ruxolitinib: 29.0%; 95 percent CI: -11.2% to +5.6%; p=0.011). Non-inferiority was not achieved for the key secondary endpoint of response rate in total symptom score (TSS). Greater improvements in all three pre-specified anemia-related secondary endpoints (proportion of patients who are transfusion independent, or transfusion dependent and transfusion rate) were observed in patients receiving momelotinib compared to ruxolitinib. However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these three additional anemia secondary endpoints. During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness and nausea; the most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache and dizziness. Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade) compared to five percent of ruxolitinib-treated patients. There was not more than Grade 3 peripheral neuropathy in momelotinib-treated patients and one case in ruxolitinib-treated patients during 24 weeks of treatment.

SIMPLIFY-2 study did not achieve its primary endpoint of superiority of momelotinib compared to BAT in patients previously treated with ruxolitinib in SRR24 (momelotinib: 6.7%; BAT: 5.8%; 95 percent CI: -8.9% to +10.2%; p=0.90). Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib; the remainder of patients received chemotherapy, interferon, corticosteroids, other therapies or some combination thereof. Differences in favor of momelotinib were observed for the pre-specified secondary endpoints of TSS and one of the three anemia-related endpoints (transfusion independence), however, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Comment;The data raise questions about momelotinib�s ability to compete against Incyte�s Jakafi.