Overview
- The FDA granted breakthrough therapy designation for INCA033989 in essential thrombocythemia with type 1 CALR mutations after failure or intolerance to at least one cytoreductive therapy, with Incyte planning a phase 3 program in 2026.
- Across phase 1 myelofibrosis studies, no dose‑limiting toxicities were observed with INCA033989 given alone or with ruxolitinib, though treatment‑emergent adverse events were common, including grade ≥3 events in 30.8% on monotherapy and 55.0% on combination.
- Monotherapy produced Week 24 spleen responses in CALR‑mutated myelofibrosis (SVR25 41.7%, SVR35 33.3%), with higher rates in JAK inhibitor–naive patients (SVR25 71.4%, SVR35 57.1%).
- Anemia responses were reported in 56% of evaluable anemic patients on monotherapy, including 40% major responses, while the ruxolitinib combination showed SVR25 and SVR35 rates of 50% and 25% with mostly stable anemia.
- Exploratory analyses showed reductions in mutant CALR variant allele frequency in 89.4% of patients with post‑baseline testing, including 10.6% with reductions of at least 25%, which the company described as consistent with potential disease‑modifying activity.