Gilead Sciences released topline data from two randomized phase 3 trials designed to evaluate its investigational JAK inhibitor momelotinib in patients with myelofibrosis, with one trial meeting its primary endpoint and the other failing to do so.
“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead, said in a Gilead-issued press release. “We plan to discuss these results with regulatory authorities to determine the next steps.”
The, double blind, active-controlled SIMPLIFY-1 study included 432 patients with myelofibrosis who had not previously been treated with a JAK inhibitor. Researchers randomly assigned patients 1:1 to momelotinib or ruxolitinib (Jakafi, Incyte) for 24 weeks.
SIMPLIFY-2 included 156 patients previously treated with, but not refractory to, ruxolitinib. Researchers randomly assigned patients 2:1 to momelotinib or best-available therapy for 24 weeks.
Splenic response rate at 24 weeks, defined as the percentage of patients who experienced at least a 35% reduction in spleen volume, served as the primary efficacy endpoint for both trials.
SIMPLIFY-1 showed momelotinib was noninferior to ruxolitinib for splenic response rate at 24 weeks. Results showed 26.5% of momelotinib-treated patients and 29% of ruxolitinib-treated patients achieved splenic response in that time (P = .011).
The trial did not meet its key secondary endpoint of noninferiority in response rate for total symptom score.
Researchers reported greater improvements in three prespecified anemia-related secondary endpoints: proportion of patients who were transfusion independent, proportion of patients who were transfusion dependent and transfusion rate. However, formal sequential statistical testing was not performed for these endpoints because total symptom score response rate did not meet the noninferiority test.
The most common adverse events in momelotinib-treated patients were thrombocytopenia, diarrhea, headache, dizziness and nausea. The most common adverse events in ruxolitinib-treated patients were anemia, thrombocytopenia, diarrhea, headache and dizziness.
A higher percentage of momelotinib-treated patients experienced any-grade peripheral neuropathy (10% vs. 5%). Researchers reported no cases of grade 3 or higher peripheral neuropathy in the momelotinib group and one such case in the ruxolitinib group.
SIMPLIFY-2 did not meet its primary endpoint of momelotinib superiority for splenic response rate at week 24 compared with best-available therapy (6.7% for momelotinib vs. 5.8% for best-available therapy).
The majority (88%) of patients assigned best-available therapy continued to receive ruxolitinib. The others received chemotherapy, corticosteroids, interferon or other therapies.
Researchers observed a benefit for momelotinib for the prespecified secondary endpoints of total symptom score and transfusion independence; however, formal sequential statistical testing was not performed because the primary superiority endpoint was not met.
Complete results from these trials will be submitted for presentation at a future scientific meeting, according to the press release.