Phase 3 VERIFY trial: rusfertide improved hematocrit control and cut phlebotomy need in polycythemia vera
In the randomized, placebo-controlled Part 1a of the phase 3 VERIFY trial, published in the Journal of Clinical Oncology, 77% of phlebotomy-dependent adults with polycythemia vera achieved a clinical response on weekly rusfertide versus 33% on placebo, with fewer phlebotomies and improved fatigue scores.
The phase 3 VERIFY trial results were published in the Journal of Clinical Oncology (Kuykendall et al, October 13, 2026) and covered by The ASCO Post on October 19. VERIFY is an international, three-part trial run at 102 centers in 19 countries. The randomized, double-blind, placebo-controlled Part 1a enrolled 293 adults with polycythemia vera who still required frequent phlebotomy despite standard-of-care treatment; 147 received weekly rusfertide and 146 received placebo, with or without concurrent cytoreductive therapy (55% were on cytoreductive therapy, 45% on phlebotomy alone).
Rusfertide is a hepcidin mimetic: a peptide that mimics the hormone hepcidin, which regulates iron availability, with the aim of limiting red blood cell production. The primary endpoint was clinical response during weeks 20 to 32, defined as absence of phlebotomy eligibility or specified intercurrent events. 77% of rusfertide patients achieved a response versus 33% on placebo (P < .0001), a 43.8 percentage-point difference (95% CI 33.5-54.2). Results were consistent in the phlebotomy-only subgroup (82% vs 33%) and the cytoreductive-therapy subgroup (73% vs 33%).
On secondary endpoints through week 32, the mean number of phlebotomies was 0.5 with rusfertide versus 1.8 with placebo (P < .0001), and 73% versus 22% of patients required no phlebotomies. Hematocrit stayed below the 45% threshold in 63% versus 14% of patients (P < .0001). Patient-reported fatigue (PROMIS Fatigue Short Form 8a, P = .0252) and overall symptom burden (Myelofibrosis Symptom Assessment Form, P = .0240) also improved significantly.
Responses proved durable: among rusfertide patients who met the primary endpoint, 84% maintained response during weeks 32 to 52, and 78% of patients who crossed over from placebo responded during weeks 40 to 52. The most common adverse events were injection-site reactions, anemia and fatigue, mostly grade 1 or 2; grade 3 adverse events occurred in 9% of rusfertide and 7% of placebo patients during the double-blind period, with no deaths reported.
Rusfertide remains an investigational medicine and is not FDA-approved; all patients continuing past week 32 receive it in an open-label extension. This brief summarizes a published trial and is not treatment guidance; decisions about polycythemia vera care belong with the treating hematologist.