NEWARK, CALIF. & OSAKA, JAPAN & CAMBRIDGE, MASS. -- Protagonist Therapeutics, Inc. (“Protagonist”) (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) announced detailed results from the Phase 3, randomized, placebo-controlled VERIFY study evaluating rusfertide in patients with polycythemia vera (PV), which met the primary and all key secondary endpoints. The data will be presented as a late-breaking oral presentation at the 61st American Society of Clinical Oncology (ASCO) Annual Meeting Plenary Session (LBA3) at 2:09 pm CDT today.

PV is characterized by overproduction of red blood cells (erythrocytosis), which may increase blood viscosity, or thickness, potentially resulting in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. People with PV can experience burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus, which may negatively impact their daily functioning and quality of life. Hematocrit is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate symptoms, but many patients still experience uncontrolled hematocrit levels with current standard of care treatments.

Rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic, is under evaluation in the Phase 3 VERIFY study for its potential to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV. In the study, patients dependent on frequent phlebotomy, with or without treatment with cytoreductive therapy, were randomized to receive once-weekly rusfertide or placebo, as an add-on to current standard of care treatment.

“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 T. Kuykendall, M.D., 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.”

The study met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during study Weeks 20-32. Study results demonstrated 76.9% of patients treated with rusfertide plus current standard of care achieved a clinical response, compared to 32.9% in the placebo plus current standard of care group (p<0.0001).1 The response observed in the rusfertide arm was consistent across subgroups, regardless of risk status or type of concurrent cytoreductive therapy.[1] In addition, all key secondary endpoints met statistical significance in favor of the rusfertide arm compared to the placebo arm in the VERIFY study, as follows:

· The mean number of phlebotomies was 0.5 phlebotomies per patient for those treated with rusfertide plus current standard of care compared to 1.8 phlebotomies per patient for those treated with placebo plus current standard of care during Weeks 0-32 (p<0.0001).[1]
- Only 27% of patients treated with rusfertide plus current standard of care required phlebotomy between Weeks 0-32, compared to 78% of patients who received placebo plus current standard of care.
- The mean number of phlebotomies during Weeks 0-32 in the rusfertide arm was reduced across subgroups, including risk status and use of concurrent cytoreductive therapy, versus the placebo arm.
· 62.6% of patients treated with rusfertide plus current standard of care maintained hematocrit levels below 45% versus 14.4% treated with placebo plus current standard of care (p<0.0001).[1]
· Rusfertide also showed statistically significant improvements in mean change from baseline to Week 32 in PROMIS Fatigue[2] (p<0.03) and the MFSAF Total Symptom Score[3] (p<0.03). Rusfertide is the first investigational therapy to prospectively demonstrate a statistically significant improvement in these patient-reported outcomes (PROs) of fatigue and symptom burden in patients with PV.[1]

Rusfertide was generally well tolerated. The majority of adverse events were low grade and non-serious and no serious adverse events considered related to rusfertide were reported. There was no evidence of increased risk of cancer in patients treated with rusfertide plus current standard of care compared to patients treated with placebo plus current standard of care at the time of the primary analysis. Cancer events were reported in one patient in the rusfertide arm (0.7%) and in seven patients in the placebo arm (4.8%). The most common treatment-emergent adverse events were localized injection site reactions (55.9%), anemia (15.9%) and fatigue (15.2%).[1]

“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 V. Patel, Ph.D., 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.”

“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 (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit (OTAU) 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 U.S. Food & Drug Administration (FDA).