Protagonist and Takeda Report Positive Phase 3 VERIFY Study Results of Rusfertide for Polycythemia Vera
Protagonist Therapeutics, Inc. and Takeda have announced positive topline results from their Phase 3 VERIFY study of rusfertide, a first-in-class investigational hepcidin mimetic peptide therapeutic, for the treatment of patients with polycythemia vera (PV), a rare blood disorder. The study, which included phlebotomy-dependent patients with PV, demonstrated that rusfertide provided significant clinical benefits compared to placebo, meeting both the primary and all four key secondary endpoints.
The VERIFY study involved 7,112 patients, who were randomized to receive either rusfertide or placebo, as an add-on to standard care. Results showed that 77% of patients treated with rusfertide achieved a clinical response—defined as the absence of phlebotomy eligibility—compared to just 33% of those receiving the placebo. This primary endpoint was met with statistical significance (p<0.0001), highlighting the potential of rusfertide to offer a meaningful treatment option for individuals with PV who struggle to control their hematocrit levels despite conventional therapies.
Rusfertide also outperformed placebo across several key secondary endpoints. The first of these, which is considered the primary endpoint for European Union regulators, demonstrated that patients in the rusfertide group required a mean of 0.5 phlebotomies per patient during the first 32 weeks of the study, compared to 1.8 phlebotomies per patient in the placebo group (p<0.0001). The other secondary endpoints, including hematocrit control, as well as patient-reported outcomes measured through the PROMIS Fatigue SF-8a and MFSAF TSS-74, showed significant improvements in those receiving rusfertide.
Safety data from the study indicated that rusfertide was generally well tolerated. The most common adverse events were mild to moderate injection site reactions, which were consistent with previous clinical studies. There were no new safety concerns identified, and no evidence of an increased cancer risk in rusfertide-treated patients compared to those on placebo.
“The positive results from the Phase 3 VERIFY study provide compelling evidence that rusfertide has the potential to address significant unmet needs in patients with PV,” said Dr. Arturo Molina, Chief Medical Officer of Protagonist Therapeutics. “We are excited to advance this first-in-class therapy, and we look forward to presenting additional details of the data at medical conferences in 2025. We extend our gratitude to the patients and investigators who contributed to this study.”
Polycythemia vera is characterized by an overproduction of red blood cells, which increases the risk of thrombosis and other cardiovascular complications. Phlebotomy, a procedure to remove excess blood to reduce hematocrit levels, is a standard method of managing PV, but it can be burdensome and often exacerbates symptoms like fatigue, visual disturbances, and iron deficiency. Despite current treatments, many patients continue to struggle with inadequate hematocrit control, which underscores the need for innovative therapies like rusfertide.
“We are encouraged by these results and the potential for rusfertide to improve the lives of patients with PV,” said Dr. Andy Plump, President of R&D at Takeda. “The clinical burden of PV, including the high treatment burden of phlebotomy, severely impacts patient quality of life. These results mark a significant step in our efforts to provide better therapeutic options for patients with blood cancers, including myeloid cancers such as PV.”
In recognition of the study’s positive results, Protagonist is set to receive a $25 million milestone payment from Takeda, as stipulated in their collaboration agreement. This marks a key milestone in the ongoing partnership between the two companies, which has already delivered promising results for PV.
“The totality of data from the VERIFY study highlights rusfertide’s potential to significantly improve patient outcomes in PV, and we look forward to working with Takeda to submit these findings to regulatory agencies,” said Dinesh V. Patel, CEO of Protagonist Therapeutics. “These results also validate Protagonist’s platform and expertise in developing highly differentiated peptide-based medicines to meet unmet medical needs.”
The VERIFY Phase 3 trial (NCT05210790) is an ongoing, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with PV. The trial is evaluating the efficacy and safety of rusfertide, administered via a once-weekly subcutaneous injection, in patients who are phlebotomy-dependent despite standard care. The study is currently in its open-label extension phase following completion of the randomized trial.
With these promising Phase 3 results, rusfertide is poised to offer a much-needed treatment option for patients with polycythemia vera who are struggling with inadequate hematocrit control. Protagonist and Takeda are now preparing to submit these findings to regulatory authorities for approval.
About Protagonist Therapeutics
Protagonist Therapeutics is a biopharmaceutical company focused on discovering and developing peptide-based therapies for unmet medical needs. Its proprietary discovery platform has enabled the development of novel peptides, including rusfertide, which is currently in Phase 3 development for PV. The company is also advancing a pipeline of innovative therapies for other rare diseases and conditions.
About Takeda
Takeda Pharmaceutical Company is a global, research-driven biopharmaceutical company committed to improving patient outcomes through the development of innovative therapies. With a strong portfolio in hematology and oncology, Takeda is dedicated to addressing the needs of patients with rare and complex diseases.
