Incyte Presents Updated Positive Data at ASH 2025 Reinforcing the Potential of INCA033989, its First-in-Class mutCALR-Targeted Monoclonal Antibody, in Patients with Essential Thrombocythemia

Core Insights - Incyte announced updated clinical data for INCA033989, a first-in-class monoclonal antibody targeting mutant calreticulin (mutCALR) for treating myeloproliferative neoplasms (MPNs) [1][2] - The data presented at the 2025 ASH Annual Meeting highlight the drug's potential for disease modification in high-risk essential thrombocythemia (ET) patients with CALR mutations [2][7] Clinical Efficacy - The studies showed rapid and durable normalization of platelet counts in ET patients treated with INCA033989, with 90% of patients on higher doses (400 to 2,500 mg) achieving a hematologic response [3] - Among these, 83.3% achieved a complete hematologic response (CHR), with nearly half (46.4%) maintaining this response for at least 12 weeks [3] - In patients on lower doses (24 to 250 mg), 88% achieved a hematologic response, with 68% achieving CHR and 44% maintaining a durable CHR [3] Molecular Response - A significant reduction in mutCALR variant allele frequency (VAF) was observed, with 96.2% of patients showing a decrease from baseline [4] - Approximately 52% of patients achieved a 25% reduction in VAF, and nearly one-third (31%) achieved a 50% reduction [4] - These reductions were noted within three to six months and were more pronounced at higher doses of INCA033989 [4] Safety Profile - INCA033989 was well tolerated across all dose levels (24 to 2,500 mg), with no dose-limiting toxicities reported [6] - The most common treatment-emergent adverse events (TEAEs) included fatigue (30.9%), headache (27.3%), upper respiratory tract infection (27.3%), and anemia (20%) [6] - Only one patient discontinued treatment due to TEAEs, and a maximum tolerated dose was not reached [6] Regulatory Status - INCA033989 received Breakthrough Therapy designation from the FDA for treating ET patients with Type 1 CALR mutations who are resistant or intolerant to prior therapies [8] - Incyte plans to initiate a registrational program for both Type 1 and non-Type 1 CALR mutations in the first half of next year [8] Background on Essential Thrombocythemia - Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of blood clots and bleeding [10] - Mutations in the CALR gene are responsible for 25-35% of ET cases, leading to abnormal blood cell production [10]