Rusfertide Meets Response End Point in Phlebotomy-Dependent Polycythemia Vera

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The addition of rusfertide to standard-of-care therapy generated an improvement in responses compared with placebo in patients with phlebotomy-dependent polycythemia vera (PV), meeting the primary end point of the phase 3 VERIFY trial (NCT05210790).¹

In an announcement from Protagonist Therapeutics and Takeda, findings showed patients treated with rusfertide experienced a clinical response rate of 77% in weeks 20 to 32 compared with 33% for those given placebo (P < .0001). A response was defined as the absence of phlebotomy eligibility.

The trial also met 4 of its key secondary end points. Patients in the rusfertide arm received a mean of 0.5 phlebotomies vs 1.8 phlebotomies for those in the placebo arm in weeks 0 to 32 (P < .0001). Statistically significant improvements were also observed for rusfertide vs placebo in regard to hematocrit control and patient-reported outcomes using PROMIS Fatigue SF-8a³ and MFSAF TSS-7⁴.

“The positive results of the phase 3 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.”

The ongoing, 3-part, global, randomized, placebo-controlled VERIFY trial 293 enrolled patients at least 18 years of age with PV per 2016 WHO criteria.^1,2 Patients needed to require at least 3 phlebotomies due to inadequate hematocrit control in 6 months prior to randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization.² Other key inclusion criteria consisted of a hematocrit of less than 45%; a white blood cell count of 4000/μL to 20,000/μL; and a platelet count of 100,000/μL to 1,000,000/μL.

Patients who were receiving cytoreductive therapy at randomization were required to be on a stable PV regimen; those being treated with phlebotomy alone needed to stop cytoreductive therapy 2 to 6 months prior to enrollment.

Key exclusion criteria consisted of clinically significant thrombosis within 2 months of randomization; active or chronic bleeding within 2 months of randomization; and a history of invasive malignancies within the last 5 years, except localized, cured prostate cancer and cervical cancer.

Patients were randomly assigned to receive rusfertide or placebo in addition to standard-of-care therapy for the first 32 weeks. All patients then received open-label rusfertide for up to 124 weeks.

Safety data for rusfertide were consistent with findings from previous clinical studies, and no new safety signals were identified.¹ Most adverse effects were grade 1 or 2 injection site reactions, and all serious AEs were not considered treatment related. Investigators reported no evidence of an increased risk of cancer in patients treated with rusfertide treated vs those given placebo.

“We are encouraged by these results and excited about the potential of rusfertide to help patients living with PV. These patients may experience a high treatment burden, and severe symptoms can impact their quality of life,” Andy Plump, MD, PhD, president of R&D at Takeda, added in a news release. “We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV.”

References

1. Protagonist and Takeda announce positive topline results from phase 3 VERIFY study of rusfertide in patients with polycythemia vera. News release. Protagonist Therapeutics and Takeda. March 3, 2025. Accessed March 3, 2025. https://www.takedaoncology.com/news/news-releases/positive-topline-results-from-verify-study/
2. A phase 3 study of rusfertide inpatients with polycythemia vera (VERIFY). ClinicalTrials.gov. Updated July 17, 2024. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT05210790