Novartis said a pivotal phase III trial of the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) has met its primary endpoint of significantly reducing spleen size in patients with myelofibrosis (MF). INC424 is a potent, selective inhibitor of the JAK1 and JAK2 tyrosine kinases.
The European study, COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy), showed treatment with INC424 provided a statistically significant reduction in spleen size in patients with primary MF, post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF), when compared with best available therapy, administered at doses and schedules determined by the investigator. The safety profile of INC424 was consistent with previous studies.
The results supported findings from another large phase III clinical trial (COMFORT-I) conducted by the collaboration partner, Incyte, in the U.S., Canada and Australia comparing treatment with INC424 to placebo in patients with MF at 24 weeks.
COMFORT-II is a randomized, open-label phase III study of INC424 versus best available therapy that enrolled 219 patients with primary MF, PPV-MF or PET-MF in 56 study locations in Europe. Two-thirds received INC424 and one-third received best available therapy, administered at doses and schedules determined by the investigator. The primary endpoint for COMFORT-II is the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline to week 48 as measured by MRI (or CT scan in applicable patients). Reduction of spleen size is an accepted measurement for clinical improvement in MF.