by David Wallace
New Treatment Targets Root Cause of ET: INCA033989 Trial Shows Powerful Results
June 15, 2025 – EHA Congress, Milan
Incyte has announced positive, late-breaking data from the first clinical studies of its experimental therapy INCA033989—an antibody designed to precisely target a genetic driver of disease in patients with Essential Thrombocythemia (ET). The results, presented today at the European Hematology Association (EHA) Annual Congress, represent a major step forward in efforts to treat ET at its source.
What Makes This Therapy Different?
Most current ET treatments aim to reduce platelet counts and manage symptoms using cytoreductive therapies. But INCA033989 aims to do more by specifically targeting and removing blood cells with the CALR mutation, which is one of the most common mutations found in ET and other myeloproliferative neoplasms (MPNs).
Key Results from the Trial:
- 86% of patients taking doses of 400mg or higher experienced a complete or partial hematologic response
- 82% of those achieved a full normalization of platelet counts
- 89% showed a reduction in the CALR mutation in their bloodstream
- 21% reached a partial molecular response after only 3 treatment cycles
A Safer, Smarter Approach?
Unlike traditional chemotherapies, INCA033989 appears to leave healthy blood-forming cells untouched while selectively wiping out CALR-mutant cells. This supports normal blood production (hematopoiesis) and may allow for long-term disease modification rather than short-term control.
The treatment was well tolerated, with no dose-limiting toxicities observed and only one patient discontinuing due to side effects. The most common side effects were mild, such as fatigue and minor respiratory infections.
Expert Insight
“These data support the hypothesis that INCA033989 has the potential not only to normalize platelet counts and provide rapid and durable hematologic responses—but to induce molecular responses, which could potentially change the natural history of the disease.”
— Dr. John Mascarenhas, Professor of Medicine, Icahn School of Medicine at Mount Sinai
Why This Matters for the ET Community
Approximately 25–35% of ET patients carry a CALR mutation. Until now, there have been no therapies specifically designed to target CALR-mutant cells. This trial offers hope that a new class of precision therapies could fundamentally change how we treat—and possibly alter the course of CALR-mutant MPNs.
What’s Next?
- Expansion of trials to include patients with myelofibrosis
- Initiation of a Phase 3 trial by early 2026
- Evaluation of combination therapy with ruxolitinib
More information: Read the full release on BusinessWire
In Plain Terms
For ET patients with the CALR mutation, this is the most exciting new therapy in clinical trials in years. It’s targeted, well-tolerated, and may actually help reverse disease progression, not just manage symptoms.
