Protagonist and Takeda Announce Positive Phase 3 VERIFY Study Results for Rusfertide in Polycythemia Vera
Protagonist Therapeutics, Inc. (“Protagonist”) (NASDAQ: PTGX) and Takeda (TSE: 4502/NYSE: TAK) have announced positive topline results from the Phase 3 VERIFY study, evaluating rusfertide in phlebotomy-dependent patients with polycythemia vera (PV). The study met its primary endpoint along with all four key secondary endpoints, highlighting rusfertide’s potential as a first-in-class investigational hepcidin mimetic peptide therapeutic. The U.S. Food & Drug Administration (FDA) has granted rusfertide Orphan Drug and Fast Track designations.
Key Study Findings
- Primary Endpoint: The study successfully met its primary endpoint, demonstrating that 77% of rusfertide-treated patients achieved clinical response, defined as the absence of phlebotomy eligibility, compared to 33% of patients in the placebo group (p<0.0001).
- EU Primary Endpoint: The first key secondary endpoint, designated as the primary endpoint for European Union (EU) regulators, was also achieved. Patients in the rusfertide group required significantly fewer phlebotomies (0.5 per patient) compared to those in the placebo group (1.8 per patient) over the 32-week period (p<0.0001).
- Additional Secondary Endpoints: Statistically significant improvements were observed in hematocrit control and patient-reported outcomes, including PROMIS Fatigue SF-8a and MFSAF TSS-7 scores.
- Safety Profile: Rusfertide was generally well tolerated, with safety results consistent with prior clinical studies. The most common adverse events were mild-to-moderate injection site reactions. No new safety concerns emerged, and there was no evidence of an increased cancer risk among rusfertide-treated patients compared to the placebo group.
Expert Commentary
Dr. Arturo Molina, Chief Medical Officer of Protagonist, stated, “The positive results of the Phase 3 VERIFY study provide compelling evidence of rusfertide’s potential as an erythrocytosis-specific treatment for PV patients who struggle with hematocrit control despite standard therapies. We plan to present further details at upcoming medical conferences in 2025. Our gratitude extends to the patients, investigators, and study personnel who contributed to the VERIFY study.”
Addressing Unmet Needs in PV Treatment
Patients with PV face an elevated risk of life-threatening cardiovascular and thrombotic events due to excessive red blood cell production. Phlebotomy, a standard treatment, can be burdensome and exacerbate symptoms such as severe fatigue, visual disturbances, and iron deficiency, significantly impacting quality of life. Current guidelines emphasize hematocrit control below 45% as a primary treatment goal. Rusfertide’s ability to reduce phlebotomy dependence presents a promising alternative for patients struggling with conventional treatments.
Dr. Andy Plump, President of R&D at Takeda, remarked, “We are encouraged by these results and excited about rusfertide’s potential to alleviate the high treatment burden associated with PV. Our commitment to developing novel therapies for blood cancers, including myeloid malignancies like PV, remains steadfast.”
Dr. Dinesh V. Patel, President and CEO of Protagonist, added, “The impressive clinical data reaffirm rusfertide’s potential to transform PV treatment. We look forward to collaborating with Takeda to advance regulatory submissions. These results mark a major milestone in Protagonist’s decade-long journey in the hepcidin program and validate our expertise in peptide-based therapeutics.”
Financial and Business Implications
Under the license and collaboration agreement between Protagonist and Takeda, Protagonist will receive a $25 million milestone payment following the successful VERIFY study results. This milestone will be payable upon completion of the clinical study report. Takeda has confirmed that these results will have an immaterial impact on its financial outlook for the fiscal year ending March 31, 2025.
Next Steps and Investor Call
Protagonist will host an investor update on Monday, March 3, 2025, at 8:30 a.m. ET to discuss the results.
Conference Call and Webcast Details:
- U.S.-Based Investors: +1 (877) 300-8521
- International Investors: +1 (412) 317-6026
- Conference Call ID: 1793905
- Webcast Link: Click Here
A replay will be available on Protagonist’s Investor Relations webpage following the event.
