Protagonist Therapeutics Inc. and Takeda have shared positive topline findings from the phase III VERIFY trial (NCT05210790), which investigated rusfertide in patients with polycythemia vera (PV) who require frequent phlebotomies. Participants were randomly assigned to receive either rusfertide or a placebo alongside standard treatment. The study successfully reached its primary objective and all four key secondary measures.¹

Rusfertide, an investigational hepcidin mimetic peptide therapy, has been designated an Orphan Drug and granted Fast Track status by the U.S. Food and Drug Administration (FDA).¹

Key Study Outcomes

• The primary endpoint was achieved, with 77% of patients receiving rusfertide showing a clinical response compared to 33% in the placebo group during weeks 20–32 (p<0.0001). Clinical response was defined as no longer meeting the criteria for phlebotomy eligibility.¹
• The first key secondary endpoint, which is the primary assessment for European Union (EU) regulators, was also met. Patients treated with rusfertide required an average of 0.5 phlebotomies, compared to 1.8 for those on placebo during weeks 0-32 (p<0.0001).¹
• The remaining three key secondary endpoints – hematocrit control and improvements in patient-reported fatigue and symptom burden measured by PROMIS Fatigue SF-8a and MFSAF TSS-7 – also reached statistical significance.¹

Rusfertide was generally well tolerated, with its safety profile aligning with prior clinical data. The most frequently observed side effects were mild-to-moderate injection site reactions. All serious adverse events were determined to be unrelated to rusfertide, and no increased cancer risk was identified in treated patients compared to the placebo group.¹

The phase III VERIFY trial is a global, randomized, placebo-controlled study involving 293 patients over a 156-week period. The trial is evaluating the efficacy and safety of once-weekly, self-administered subcutaneous rusfertide in patients who continue to require phlebotomy despite standard treatment, such as hydroxyurea, interferon, or ruxolitinib.²

All patients have now completed the randomized, placebo-controlled segment of the study and have transitioned to the open-label phase.

“The positive results of the phase III VERIFY study across the primary and all key secondary end points provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard-of-care treatments,” Arturo Molina, MD, MS, chief medical officer of Protagonist, stated in a news release. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.”²

References

1. PharmaWand. Positive results from phase III VERIFY study of rusfertide to treat phlebotomy-dependent patients with polycythemia vera.- Protagonist Therapeutics + Takeda. Available at: https://www.pharmawand.co.uk/members/news.aspx?entityID=26861&alrtPrfID=1589 (Date last accessed: 13 March 2025)
2. Tekeda. Protagonist and Takeda announce positive topline results from phase 3 VERIFY study of rusfertide in patients with polycythemia vera. Available at: https://www.takeda.com/newsroom/newsreleases/2025/positive-topline-results-from-verify-study/ (Date last accessed: 13 March 2025)

Oncology Nursing News. Rusfertide plus SOC reaches response end point in phlebotomy-dependent PV. Available at: https://www.oncnursingnews.com/view/rusfertide-plus-soc-reaches-response-end-point-in-phlebotomy-dependent-pv (Date last accessed: 13 March 2025)

Disclosure: This article was created by the touchHAEMATOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

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