Rusfertide Earns FDA Priority Review in Polycythemia Vera

The FDA has granted priority review to a new drug application (NDA) seeking approval for rusfertide as a treatment for patients with polycythemia vera, according to a press release from the developers, Takeda and Protagonist Therapeutics.¹

Developers originally submitted the NDA for rusfertide as a treatment for this patient population in January 2026.² The FDA has set a Prescription Drug User Fee Act date within the third quarter of 2026 for approving the investigational hepcidin mimetic peptide therapeutic.

“There is an urgent need for innovative treatment options in polycythemia vera, where patients currently [have] limited therapeutic choices to control their hematocrit and significant symptom burden,” Andy Plump, MD, PhD, president of Research & Development at Takeda, stated in the press release.¹ “The FDA’s acceptance of our NDA brings us closer to potentially offering a first-in-class therapy that could meaningfully improve clinical outcomes and quality of life.”

Supporting data for the NDA primarily came from the phase 3 VERIF Y trial (NCT05210790) evaluating rusfertide among 293 patients with polycythemia vera. Additionally, the NDA contains data from the phase 2 REVIVE study (NCT04057040) and the long-term extension THRIVE study (NCT06033586).

VERIFY Study

The 32-week primary analysis, which investigators presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that 76.9% of patients who received rusfertide achieved a clinical response compared with 32.9% in the standard-of-care arm (P <.0001).³ Data also showed a mean number of phlebotomies of 0.5 vs 1.8 in each arm from weeks 0 to 32 (P <.0001), and 62.6% vs 14.4% of patients maintained hematocrit levels below 45% (P <.0001). Treatment with rusfertide was typically well tolerated at the time of analysis.

Updated findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition showed that, after 52 weeks, 61.9% of patients who received rusfertide plus standard of care had an enduring clinical response, defined as the absence of phlebotomy eligibility.⁴ Moreover, 84.1% of patients who experienced a clinical response on rusfertide during weeks 20 to 32 sustained their response. Among those who crossed over from placebo to rusfertide at week 32, 77.9% experienced a clinical response.

The ongoing, 3-part, international VERIFY trial is assessing treatment with rusfertide across 156 weeks, with potential treatment extension for patients who have sustained benefit beyond this period. Investigators are evaluating the safety and efficacy of once-weekly subcutaneous rusfertide among patients with uncontrolled hematocrit and dependence on phlebotomy despite current standard-of-care options such as phlebotomy, hydroxyurea, interferon, and/or ruxolitinib (Jakafi).

The trial’s primary end point is the rate of patients who achieve a response from weeks 20 to 32 and fulfill the absence of phlebotomy eligibility; being eligible for phlebotomy was marked by a confirmed hematocrit of at least 45% that was 3% or higher than their baseline hematocrit value, or a hematocrit of 48% or higher. All patients have completed the randomized, placebo-controlled portion of the trial and are eligible for treatment during the open-label parts of the study.

REVIVE/THRIVE Studies

Investigators of the phase 2 REVIVE trial assessed rusfertide in adults with polycythemia vera across 3 parts: the dose-finding part 1 component (n = 70); the placebo-controlled, blinded, randomized part 2 component (n = 59); and the open-label part 3 component (n = 58). The ongoing, open-label expansion THRIVE study is investigating the long-term durability of response and safety of rusfertide among 46 patients who previously participated in the REVIVE study. The THRIVE study is further evaluating the maintenance of hematocrit control, reductions in therapeutic phlebotomy needs, and safety of subcutaneous rusfertide over an additional 2-year period.

After crossing over from REVIVE to THRIVE, patients who received continued rusfertide with or without cytoreductive therapy experienced a more than 13-fold reduction their estimated annual therapeutic phlebotomy rate vs baseline prior to entering the REVIVE trial.⁴ The mean annualized phlebotomy rate decreased from 9.2 phlebotomies per year at baseline to 0.7 phlebotomies per year. Additionally, the safety profile of rusfertide in the THRIVE study was comparable with prior reports of the agent.

References

1. Takeda and Protagonist announce U.S. Food and Drug Administration accepts new drug application and grants priority review for rusfertide as a potential first-in-class therapy for polycythemia vera. News release. Takeda. March 2, 2026. Accessed March 2, 2026. https://tinyurl.com/3njzamwp
2. Takeda and Protagonist announce submission of new drug application (NDA) for rusfertide for treatment of polycythemia vera (PV). News release. Takeda and Protagonist Therapeutics. March 2, 2026. Accessed January 6, 2026. https://tinyurl.com/bde99y9j
3. Protagonist and Takeda announce ASCO plenary presentation highlighting full 32-week results from phase 3 VERIFY study of rusfertide, showing reductions in phlebotomy, improved hematocrit control in polycythemia vera. News release. Takeda and Protagonist Therapeutics. June 1, 2025. Accessed March 2, 2026. https://tinyurl.com/3fmnwpyz
4. Protagonist and Takeda present longer-term data at ASH 2025 showing rusfertide delivers durable response and hematocrit control in polycythemia vera. News release. Takeda and Protagonist Therapeutics. December 6, 2025. Accessed March 2, 2026. https://tinyurl.com/5n9ahj8r