Myelofibrosis is a rare hematological malignancy with limited therapeutic options and significant unmet clinical need. Current first line therapy options are two Janus kinase (JAK) inhibitors (JAKis), Incyte’s Jakavi/Jakafi (ruxolitinib) and Impact Biomedicine’s Inrebic (fedratinib). Jakafi has dominated the myelofibrosis market since its launch in 2011 and has seen lucrative financial returns, achieving blockbuster status. However, Jakafi is not a curative agent. Since patients often discontinue the treatment and experience exacerbated anemia, clinicians prescribe additional lines of therapy. Several pipeline JAKis have entered Phase III trials, seeking to expand the lines of therapy by targeting Jakafi-refractory patients, capitalizing on a currently underserved patient population.
Notably, topline data have recently been released from the randomized, double-blind, active control Phase III MOMENTUM study comparing the selective JAK1, JAK2 and ACVR1 inhibitor, Sierra Oncology’s momelotinib, versus the anti-anemia molecule danazol. In Jakafi-refractory patients, momelotinib achieved all prespecified primary and secondary endpoints. A total of 25% (n=130) of patients experienced a total symptom score (TSS) reduction of ≥50% on momelotinib, demonstrating clear superiority to danazol (TSS reduction ≥50% in 9% of patients). Momelotinib was also superior in splenic response rate (SRR) compared to danazol (23% versus 3%) and demonstrated promising safety data with 54% of patients experiencing grade 3 or higher toxicities, compared to 65% on danazol.