Protagonist posts results of Phase 3 rusfertide study in polycythemia vera

Protagonist Therapeutics, Inc. has posted results for a Phase 3 study of rusfertide in adults with polycythemia vera (PV). The trial registry record for NCT05210790, which uses the acronym VERIFY, lists the results as first posted on October 19, 2026. For the primary outcome, the record lists response for 32.9% of participants on placebo and 76.9% on rusfertide.

What the record says about the design

The record calls the study A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300; TAK-121) in Patients With Polycythemia Vera. It lists the design as randomized, parallel, with triple masking of the participant, the investigator and the outcomes assessor. The record lists 293 participants. It says they took part across 102 sites starting on 11 April 2022.

The record says PV is a long-term condition in which the bone marrow makes too many red blood cells. It says treatment aims to keep the percentage of red blood cells in the blood, called hematocrit, below 45%. Many people with PV are treated with blood removal, called phlebotomy. The record says rusfertide works like hepcidin, a natural hormone that helps control iron levels in the body.

The study has 4 parts:

Part 1a: participants received rusfertide or placebo once weekly by subcutaneous injection, from baseline up to Week 32.
Part 1b: all participants received rusfertide, from Weeks 32 to 52, in an open-label period.
Part 2: a long-term extension from Weeks 52 to 156.
Part 3: continued rusfertide treatment from Week 156 to the end of the study, approximately 5 years.

In Part 1a, participants kept their ongoing therapy for PV and added rusfertide or rusfertide-matching placebo. Rusfertide doses were titrated to maintain hematocrit below 45%. The starting dose was 19 mg. The record lists the Part 1a doses as 9.5, 19, 28, 41, 54, 69 and 82 mg.

To take part, adults needed a diagnosis of PV under the revised 2016 World Health Organization criteria. Participants also needed at least 3 phlebotomies due to inadequate hematocrit control in the 28 weeks before randomization, or at least 5 in the year before randomization.

The primary outcome

The record lists one primary outcome: the percentage of participants who achieved response in Part 1a, from Weeks 20 to 32. It defines response as the absence of phlebotomy eligibility. Phlebotomy eligibility was either a confirmed hematocrit of at least 45% that was at least 3% higher than the baseline hematocrit, where confirmation meant 2 consecutive assessments, or a hematocrit of at least 48%.

The record posts the result for the intent-to-treat set, which comprised all randomized participants according to the treatment assigned. It lists 146 participants on placebo and 147 on rusfertide. Response was 32.9% on placebo and 76.9% on rusfertide.

The record lists a superiority comparison using the Cochran-Mantel-Haenszel test, stratified by ongoing PV therapy. It lists an odds ratio of 6.42 (95% confidence interval 3.81 to 10.80) and a p-value of <0.0001.

The secondary outcomes

The record also lists secondary outcomes, among them the number of phlebotomies, the percentage of participants with all hematocrit values below 45%, and patient-reported fatigue and symptom scores. The registry lists the results for these outcomes as not posted, with an anticipated posting date of 2029-08.

Participant flow and safety counts

In the Part 1a double-blind period, the record lists 146 participants starting on placebo and 147 on rusfertide. It lists 141 completing on placebo and 134 on rusfertide. Not completing were 5 on placebo and 13 on rusfertide. Adverse events were the reason for 4 on placebo and 8 on rusfertide. The record lists 2 participants on rusfertide as randomized but not treated.

The adverse event tables list deaths as 0 in each group. For Part 1a, serious adverse events affected 7 of 146 participants on placebo and 5 of 145 on rusfertide. In Part 1b, serious adverse events affected 7 of 274. In Part 2, they affected 10 of 266.

The record says adverse events are still being collected and will be updated one year after the study completion date.

What the record says about status

The record lists the overall status as active, not recruiting. It says Part 2 is ongoing and Part 3 has not started as of the data cutoff date of 21 February 2025, so data for Part 3 is not included. The record says the results posted here are the primary results.