Beyond Phlebotomy: Rusfertide’s Data Signals a New Era for Polycythemia Vera Treatment
For the vast majority of patients battling polycythemia vera (PV), a chronic blood cancer, the routine of phlebotomy – having blood drawn to reduce cell count – has been a lifelong necessity. But new data presented at the American Society of Hematology (ASH) Annual Meeting is challenging that paradigm. Results from the Phase 3 VERIFY study demonstrate that rusfertide, an investigational therapy, allowed a significant portion of patients to maintain hematocrit control and, crucially, largely avoid phlebotomy for up to 52 weeks.
Understanding Polycythemia Vera and the Limitations of Current Treatment
Polycythemia vera isn’t simply about having “too much blood.” It’s a bone marrow disorder leading to an overproduction of red blood cells, thickening the blood and dramatically increasing the risk of dangerous blood clots, heart attacks, and strokes. Beyond these severe risks, patients often endure debilitating fatigue, dizziness, and headaches, severely impacting their quality of life. Current treatment relies on phlebotomy, often combined with medication, but neither addresses the underlying cause of the disease. Phlebotomy, while effective at reducing blood thickness, is a burdensome and often painful process, potentially damaging veins over time.
How Rusfertide Works: Mimicking the Body’s Natural Regulator
Rusfertide represents a fundamentally different approach. Developed by Protagonist Therapeutics in partnership with Takeda Oncology, it’s a hepcidin mimetic peptide. Hepcidin is a naturally occurring hormone that regulates iron levels in the blood, and consequently, red blood cell production. Rusfertide essentially replicates this process, helping patients maintain a healthy hematocrit level – ideally at or below 45% – without relying on repeated blood removal. This targeted approach addresses the root of the problem, rather than just managing the symptoms.
Long-Term Data: VERIFY and THRIVE Studies Paint a Promising Picture
The encouraging 52-week data from VERIFY builds on earlier findings from the THRIVE long-term extension study, providing nearly five years of data for some patients. According to Teresa Bitetti, President of Global Oncology at Takeda, this extended observation period reveals the sustained benefits of rusfertide. “These benefits for patients were then maintained through at least 1 year in VERIFY and up to 4 years in the THRIVE long-term extension study,” stated Arturo Molina, MD, MS, Chief Medical Officer for Protagonist Therapeutics. The THRIVE data, in particular, showed a remarkable greater than 13-fold reduction in annualized phlebotomy rate – dropping from an average of 9.2 phlebotomies per year to just 0.7.
Key Findings from the VERIFY Study at 52 Weeks
The latest results presented at ASH highlight the durability of rusfertide’s effects:
- 61.9% of patients treated with rusfertide alongside standard care throughout the 52 weeks achieved a durable clinical response, defined as avoiding the need for phlebotomy.
- 84.1% of patients who initially responded to rusfertide (weeks 20-32) maintained that response.
- 77.9% of patients who switched from placebo to rusfertide at week 32 experienced a clinical response during the subsequent evaluation period.
- The median time to first phlebotomy was not reached in either rusfertide group, or in those who crossed over from placebo.
Beyond Hematocrit: Improving Quality of Life
The benefits of rusfertide extend beyond simply avoiding phlebotomy. Patients reported significant improvements in quality of life, particularly in alleviating the debilitating fatigue often associated with PV. As Bitetti emphasized, this isn’t just about numbers; it’s about restoring a sense of normalcy for patients who often struggle with “can’t get out of bed fatigue.” Reducing thrombotic events, a serious complication of PV, is another key benefit, with THRIVE data demonstrating a substantial reduction compared to the natural course of the disease. Learn more about PV from the National Cancer Institute.
What’s Next for Rusfertide and the Future of PV Treatment?
With breakthrough therapy designation granted by the FDA in August 2025, Takeda anticipates filing for approval by the end of the year. If approved, rusfertide could represent a paradigm shift in how PV is managed, moving away from symptom management towards a more targeted, disease-modifying approach. Ongoing subgroup analyses are exploring the therapy’s effectiveness across different patient populations, but initial findings suggest consistent benefits. The long-term data from VERIFY and THRIVE are particularly compelling, suggesting that rusfertide’s benefits are not just immediate, but sustained over years.
The success of rusfertide also opens the door for further research into hepcidin mimetics for other iron-related disorders. Could this approach be adapted to treat iron deficiency anemia, or even certain types of cancer? The potential is significant, and the data from rusfertide are paving the way for a new generation of therapies focused on regulating iron homeostasis.
What are your thoughts on the potential impact of rusfertide on the treatment of polycythemia vera? Share your perspective in the comments below!
