Phase III Data on Momelotinib for Myelofibrosis Is Mixed

The results from two phase III trials of the investigational JAK1/2 inhibitor momelotinib for patients with myelofibrosis (MF) had variable outcomes.

In the double-blind, active-controlled, randomized SIMPLIFY-1 study (which included 432 patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF), momelotinib achieved its primary endpoint of non-inferiority to ruxolitinib for splenic response rate at week 24 (SSR24; defined as the percentage of patients experiencing a ≥35% reduction in spleen volume): 26.5 percent for momelotinib compared with 29 percent for ruxolitinib (95% CI −11.2-5.6; p=0.011). However, non-inferiority was not demonstrated for response rate in total symptom score (TSS) at week 24 (secondary endpoint; defined as the percentage of patients reaching ≥50% reduction in their symptoms).

The most common adverse events (AEs) associated with momelotinib in SIMPLIFY-1 included thrombocytopenia, diarrhea, headache, dizziness, and nausea, while the most common AEs associated with ruxolitinib included anemia, thrombocytopenia, diarrhea, headache, and dizziness.

In the randomized SIMPLIFY-2 study (which included 156 patients with MF who had previously received, but were not refractory to, ruxolitinib) treatment with momelotinib was not shown to be superior to best available therapy (BAT) for SSR24 (the study’s primary endpoint): 6.7 percent for momelotinib compared with 5.8 percent for BAT (95% CI −8.9-10.2; p=0.9).

Sources: Gilead Sciences news release, November 16, 2016; Fierce Biotech, November 17, 2016.