Momelotinib is a JAK1/JAK2 and ACVR1 inhibitor approved for the treatment of myelofibrosis in patients with anemia. Unlike other JAK inhibitors, it uniquely targets anemia by reducing hepcidin levels, improving erythropoiesis alongside spleen and symptom control. Anemia, particularly when moderate (Hb ≥8 to <10 g/dL) or severe (Hb <8 g/dL), is a significant negative prognostic factor in myelofibrosis. While severe anemia is typically prioritized in treatment, the implications of moderate anemia and early correction have been underexplored. This post hoc analysis from the Phase III SIMPLIFY-1 (JAK inhibitor–naive) and MOMENTUM (JAK inhibitor–experienced) trials evaluated the impact and kinetics of achieving hemoglobin >10 g/dL with momelotinib in patients with baseline (BL) moderate vs. severe anemia.

Momelotinib led to faster and more frequent achievement of Hb >10 g/dL in patients with BL moderate anemia compared to those with severe anemia. In SIMPLIFY-1, 69% with moderate and 50% with severe anemia reached this target by week 24; mean times to response were 1.2 and 2.1 months, respectively. In MOMENTUM, these figures were lower but consistent (47% vs. 24%; 1.0 vs. 1.7 months). Longitudinally, the majority of patients with moderate anemia eventually crossed the 10 g/dL threshold (83% in SIMPLIFY-1; 48% in MOMENTUM), supporting momelotinib’s efficacy. Notably, achieving Hb >10 g/dL was numerically linked to longer overall survival across both studies, regardless of JAK inhibitor exposure or anemia severity at baseline. These findings reinforce the clinical value of early anemia correction in myelofibrosis and position momelotinib as a disease-modifying therapy capable of delivering hematologic and survival benefits.

KOL insights

“This post hoc analysis demonstrates that across all 3 Phase III trials of momelotinib in myelofibrosis to date, at least 75% of patients treated with momelotinib either maintained or experienced improved transfusion intensities vs baseline, these results provide evidence that underscores the consistent anemia benefits provided by momelotinib for the majority of patients.”– Expert Opinion

Conclusion

Janus kinase (JAK) inhibitors have become a mainstay therapy for various cancers, including myelofibrosis. At present, four JAK inhibitors are authorized for the management of Myelofibrosis. The myelofibrosis treatment landscape is led by JAK inhibitors—JAKAFI (ruxolitinib, Incyte), INREBIC (fedratinib, BMS), OJJAARA (momelotinib, GSK), and VONJO (pacritinib, CTI/BMS)—each targeting distinct patient subsets. However, limitations in durability, cytopenias, and resistance have opened space for next-wave assets. Emerging therapies like pelabresib (BET), navitoclax (BCL-2), nuvisertib (PIM1), and bomedemstat (LSD1) aim to enhance or replace JAKi efficacy through complementary mechanisms. With combination strategies gaining traction, competition is intensifying around differentiation via disease modification, symptom control, and hematologic recovery.  JAKAFI is anticipated to lose patent protection in 2027 for Novartis and in 2028 for Incyte, which provides a competitive advantage to OJJAARA. OJJAARA is projected to achieve the highest revenue among its peers, reaching approximately USD 1,470 million by 2034 across the 7MM.