FDA Grants Breakthrough Therapy Status to Incyte’s First-in-Class mutCALR Antibody
Incyte has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to INCA033989, a first-in-class monoclonal antibody targeting mutant calreticulin (mutCALR).
The therapy is intended for patients with essential thrombocythemia (ET) carrying a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive treatment.
Essential thrombocythemia is a chronic blood disorder characterised by persistently elevated platelet counts caused by abnormal bone marrow activity.
CALR mutations are the second most common driver of ET, present in around 25% of patients. Type 1 CALR mutations, a 52-base pair deletion, account for 55% of CALR mutations and carry the highest risk of progression to myelofibrosis.
The Breakthrough Therapy designation is based on early Phase 1 data showing that INCA033989 was well-tolerated and rapidly normalised platelet counts, with higher doses producing stronger responses across mutation types.
Incyte plans to start a Phase 3 programme for all CALR mutation types in mid-2026, following regulatory alignment. Updated Phase 1 results will be presented at the 2025 ASH Annual Meeting in December.
INCA033989 represents a first-in-class approach to selectively target malignant cells in mutCALR ET, potentially offering a novel treatment for patients with limited options and addressing an unmet medical need.
