Rusfertide Demonstrates Sustained Efficacy in 52-Week Polycythemia Vera Study, Supporting Regulatory Filing
Key Insights
Extended 52-week data from the Phase 3 VERIFY study showed 61.9% of polycythemia vera (search) patients treated with rusfertide maintained absence of phlebotomy eligibility from baseline to Week 52.
Patients who crossed over from placebo to rusfertide at 32 weeks achieved a 77.9% response rate, demonstrating consistent efficacy across treatment groups.
Four-year data from the THRIVE extension study revealed a 13-fold reduction in annual phlebotomy rates compared to baseline, with mean rates dropping from 9.2 to 0.7 phlebotomies per year.
Protagonist Therapeutics and Takeda (search) have presented compelling 52-week data from their pivotal Phase 3 VERIFY study of rusfertide in polycythemia vera (search) (PV) patients at the 67th American Society of Hematology Annual Meeting, demonstrating sustained efficacy and supporting the companies' planned regulatory submission by the end of 2025.
The extended analysis revealed that 61.9% of patients continuously treated with rusfertide plus current standard of care maintained absence of phlebotomy eligibility from baseline to Week 52, reinforcing the drug's potential as a durable treatment option for this rare blood disorder. The study's crossover design provided additional validation, with 77.9% of patients who switched from placebo to rusfertide at Week 32 achieving clinical response during the assessment window of Weeks 40-52.
Sustained Hematocrit Control and Clinical Response
The VERIFY study enrolled 293 patients with uncontrolled hematocrit who remained phlebotomy-dependent despite receiving current standard of care treatments including hydroxyurea, interferon, and/or ruxolitinib. During the initial 32-week randomized phase, 147 patients received rusfertide while 146 received placebo, both as add-on therapy to existing treatments.
"The 52-week data demonstrated the sustained efficacy of rusfertide, reducing the need for patients to receive phlebotomy while maintaining hematocrit control," said Dr. Andrew T. Kuykendall, VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "The 32-week VERIFY primary results were already promising, and this deeper understanding of the durability of response with rusfertide is critical to inform clinical decision-making for polycythemia vera (search)."
Key efficacy metrics demonstrated rusfertide's sustained benefit across multiple parameters. Among patients who achieved clinical response during the initial assessment window (Weeks 20-32), 84.1% maintained their response through Week 52. Mean hematocrit levels remained below 43% throughout the 52-week period in patients treated with rusfertide, while the median time to first hematocrit ≥45% was not reached in the rusfertide group during either study phase.
Long-Term Extension Data Reinforces Durability
The durability findings were further supported by four-year data from 46 patients who transitioned from the Phase 2 REVIVE study to the long-term extension THRIVE study. These patients demonstrated a remarkable 13-fold reduction in estimated annual therapeutic phlebotomy rates compared to baseline, with mean annualized rates decreasing from 9.2 phlebotomies per year before study entry to 0.7 phlebotomies per year during THRIVE treatment.
This dramatic reduction in phlebotomy requirements addresses a critical unmet need in PV management, where achieving and maintaining controlled hematocrit levels below 45% represents the primary treatment goal to prevent life-threatening thrombotic events such as stroke (search), deep vein thrombosis (search), and pulmonary embolism (search).
Safety Profile Supports Continued Development
Rusfertide maintained a well-tolerated safety profile through 52 weeks of treatment. The most common treatment-emergent adverse events included injection site reactions (47.4%), anemia (search) (25.6%), and fatigue (19.6%), which were primarily grade 1 or 2 in severity. Serious adverse events occurred in 8.1% of rusfertide-treated patients, with no new safety signals identified in the extended follow-up period.
Quality of life measures also showed sustained improvement, with patients maintaining benefits in patient-reported outcomes as measured by PROMIS Fatigue SF-8a and MFSAF TSS7 scales throughout the treatment period.
Regulatory Path Forward
"The totality of these data further demonstrates rusfertide's well tolerated safety profile and ability to deliver durable hematocrit control and clinical response as defined by absence of phlebotomy eligibility and support its potential to expand the treatment armamentarium for PV," said Arturo Molina, Chief Medical Officer at Protagonist. "We look forward to continuing to work with our partner, Takeda (search), to prepare for submission of an NDA to the FDA."
Rusfertide, a mimetic of the natural hormone hepcidin, has received multiple regulatory designations from the FDA including Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation, reflecting the significant unmet medical need in polycythemia vera (search) treatment.
"We are committed to making a difference for patients with PV who face serious risks from thrombotic events if they are unable to adequately control hematocrit levels with currently available treatment options," said Dr. Phuong Khanh Morrow, Head of the Oncology Therapeutic Area Unit at Takeda (search). "The comprehensive data presented at ASH, from the pivotal VERIFY and long-term THRIVE studies, strongly underscore the potential of rusfertide to provide a sustained response, addressing a critical unmet need in managing this chronic cancer."
The companies plan to submit a New Drug Application to the FDA by the end of 2025, with Protagonist remaining primarily responsible for development through NDA filing under their worldwide collaboration and license agreement with Takeda (search) entered in 2024.