Takeda and Protagonist Announce Submission of Rusfertide NDA for Polycythemia Vera

On January 5, 2026, Takeda and Protagonist Therapeutics announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for rusfertide for the treatment of polycythemia vera (PV) in adult patients.1

The submission is based on a positive 32-week primary analysis and 52-week results from the phase 3 VERIFY study. This ongoing program is following patients receiving rusfertide plus standard of care for a total of 124 weeks. Data from the first phase of the trial have been previously reported, highlighting rusfertide’s efficacy and safety in reducing phlebotomy reliance in patients with PV.1

“Rusfertide has the potential to redefine the treatment paradigm for PV by offering patients a novel, first-in-class erythrocytosis-specific therapy that significantly reduces or eliminates the need for frequent phlebotomy,” Dinesh Patel, PhD, president and chief executive officer of Protagonist, said in a statement. “Submitting this NDA marks a major inflection point in the decade-long journey that started with a hepcidin mimetic program at Protagonist. Rusfertide has practice-changing potential that could become standard of care for patients with PV who currently rely on burdensome and often ineffective therapies.”1

Rusfertide is a first-in-class investigational subcutaneous treatment that mimics hepcidin, a naturally produced hormone that regulates iron homeostasis and production of red blood cells. The drug aims to reduce excess red blood cell production by targeting iron dysregulation in PV, helping patients to achieve sustained hematocrit control. Rusfertide has previously received Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation from the FDA.1

The VERIFY trial is an ongoing 3-part, global, randomized, placebo-controlled phase 3 study, evaluating rusfertide in patients with PV over a 156-week period. The study aims to determine the efficacy and safety of once-weekly subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment.1

Investigators included patients aged ≥18 years with ≥3 phlebotomies due to inadequate hematocrit control within 6 months prior to randomization or ≥5 phlebotomies in 1 year prior to randomization. Additionally, patients were required to exhibit CBC values as follows:

1. Hematocrit <45%
2. White blood cell 4000/µL to 20,000/µL (inclusive)
3. Platelets 100,000/µL to 1,000,000µL (inclusive)

Patients were excluded from the trial if they had clinically meaningful laboratory abnormalities at screening, if they required phlebotomy at hematocrit levels <45%, or if they had clinically significant thrombosis within 2 months prior to randomization, among other criteria.2

A total of 293 patients were ultimately enrolled; during the first phase, they were randomly assigned to either rusfertide or placebo for 32 weeks, plus standard of care. This first phase met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during weeks 20-32. 76.9% of patients treated with rusfertide plus current standard of care achieved this clinical response, compared to 32.9% among placebo recipients (P <.0001). Additionally, 62.6% of patients treated with rusfertide maintained hematocrit levels <45% compared to 14.4% of placebo recipients (P <.0001).2,3

The ongoing open-label phase 2 saw all patients who completed part 1 receive rusfertide treatment for 124 weeks. A total of 274 patients continued into part 2 and 267 remained on through week 52. Data from the first 52 weeks have been reported, highlighting a maintained clinical response. 61.9% of patients treated with rusfertide plus current standard of care in part 2 exhibited a durable response; of these, 77.9% of patients who crossed over from placebo experienced a clinical response during the assessment window of weeks 40-52.4

“This is an important milestone toward our goal of addressing critical gaps that patients living with polycythemia vera face today,” Teresa Bitetti, president of the Global Oncology Business Unit, Takeda, said in a statement. “The comprehensive VERIFY study data underscore rusfertide’s strong clinical profile and potential to provide sustained hematocrit control while reducing phlebotomy and symptom burden.”1

References

1. Takeda Pharmaceutical Company. Takeda and Protagonist Announce Submission of New Drug Application (NDA) for Rusfertide for Treatment of Polycythemia Vera (PV). BusinessWire. January 5, 2026. Accessed January 5, 2026. https://www.businesswire.com/news/home/20260101831438/en/Takeda-and-Protagonist-Announce-Submission-of-New-Drug-Application-NDA-for-Rusfertide-for-Treatment-of-Polycythemia-Vera-PV

2. Protagonist Therapeutics, Inc. A Phase 3 Study of Rusfertide in Pateints With Polycythemia Vera (VERIFY). ClinicalTrials.gov: NCT05210790. Updated August 7, 2025. Accessed January 5, 2026. https://clinicaltrials.gov/study/NCT05210790

3. Takeda Pharmaceutical Company. 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. June 1, 2025. Accessed January 5, 2026. https://www.takeda.com/newsroom/newsreleases/2025/polycythemia-vera-rusfertide-study/

4. Takeda Pharmaceutical Company. Protagonist and Takeda Present Longer-Term Data at ASH 2025 Showing Rusfertide Delivers Durable Response and Hematocrit Control in Polycythemia Vera. December 6, 2025. Accessed January 5, 2026. https://www.takeda.com/newsroom/newsreleases/2025/ash-rusfertide/