Protagonist and Takeda have shared full 32-week results from the Phase 3 VERIFY study of rusfertide in patients with polycythemia vera (PV), demonstrating significantly improved clinical outcomes over placebo. The data were presented as a late-breaking oral presentation at the 61st American Society of Clinical Oncology (ASCO) Annual Meeting plenary session.

The VERIFY study, a randomized, placebo-controlled trial, met its primary and all key secondary endpoints. It showed that rusfertide, added to standard of care, reduced phlebotomy eligibility and improved hematocrit control in both high- and low-risk PV patients. The therapy, a first-in-class hepcidin mimetic peptide, is designed to regulate iron homeostasis and red blood cell production.

“PV poses significant challenges for patients, including debilitating symptoms and the risk of serious thrombotic events, and hematocrit control is crucial to improving patient outcomes. The VERIFY study demonstrated that treatment with rusfertide controls hematocrit levels in phlebotomy-dependent patients, including patients receiving cytoreductive therapies,” said Dr. Andrew Kuykendall, VERIFY lead investigator and associate member in the department of hematology at Moffitt Cancer Center.

“These results suggest rusfertide has the potential to become part of the standard of care treatment for patients with PV.”

PV is marked by excess red blood cell production, increasing the risk of life-threatening complications such as stroke or deep vein thrombosis. Despite current therapies, many patients still experience uncontrolled hematocrit levels. Rusfertide is being evaluated as an add-on to standard treatment in patients who require frequent phlebotomy, with or without concurrent cytoreductive therapy.

“These findings underscore rusfertide’s potential as a first-in-class erythrocytosis-specific treatment for PV and validate more than a decade of scientific innovation originating from Protagonist’s peptide technology platform,” said Dinesh Patel, president and chief executive officer at Protagonist.

“We would like to thank all the patients, study staff and investigators for participating in the VERIFY study. We are pleased to partner with Takeda as we continue to advance rusfertide to potentially transform the standard of care in PV patients around the world.”

The primary endpoint, clinical response defined by absence of phlebotomy eligibility between weeks 20 and 32, was achieved by 76.9% of patients in the rusfertide arm versus 32.9% in the placebo arm (p<0.0001). This benefit was seen across risk groups and regardless of concurrent therapies.

All key secondary endpoints met statistical significance in favor of rusfertide.

These included:

• The mean number of phlebotomies was 0.5 per patient in the rusfertide group versus 1.8 per patient in the placebo group between weeks 0–32.
• Only 27% of patients receiving rusfertide required phlebotomy during the trial compared to 78% in the placebo group.
• 62.6% of rusfertide-treated patients maintained hematocrit levels below 45%, compared to 14.4% in the placebo group (p<0.0001).
• Rusfertide showed statistically significant improvements in patient-reported outcomes including PROMIS Fatigue and MFSAF total symptom score.

The therapy was generally well tolerated. Most adverse events were low grade and non-serious, and no serious adverse events considered related to rusfertide were reported. Rates of cancer events were lower in the rusfertide arm compared to placebo.

“These promising pivotal data strongly support rusfertide’s potential benefit for a broad spectrum of patients with PV who may be receiving current standard of care therapies but not achieving adequate hematocrit control,” said Phuong Khanh Morrow, head of the oncology therapeutic area unit at Takeda.

“We look forward to receiving additional data from the VERIFY trial later this year, advancing rusfertide towards regulatory approval and continuing our collaboration with Protagonist to bring this innovative therapy to patients.”

Rusfertide has received orphan drug designation and fast track designation from the FDA.