Rusfertide, a novel hepcidin mimetic developed by Protagonist Therapeutics in collaboration with Takeda, has demonstrated positive topline results in the Phase 3 VERIFY trial for patients with polycythemia vera (PV). The study, a randomized, placebo-controlled trial, met its primary endpoint, showing a statistically significant reduction in the need for phlebotomies among patients treated with rusfertide compared to placebo.
The VERIFY trial (NCT05210790) randomized phlebotomy-dependent PV patients to receive either rusfertide or placebo as an add-on to standard-of-care treatment. The primary endpoint was the proportion of patients achieving a response, defined as the absence of phlebotomy eligibility during weeks 20-32. Results showed that 77% of rusfertide-treated patients achieved a clinical response, compared to only 33% in the placebo group (p<0.0001).
Key Secondary Endpoints Met
In addition to the primary endpoint, the VERIFY trial also met all four key secondary endpoints. Notably, the mean number of phlebotomies per patient during weeks 0-32 was 0.5 in the rusfertide arm versus 1.8 in the placebo arm (p<0.0001). The other three pre-specified key secondary endpoints, namely hematocrit control and patient-reported outcomes using PROMIS Fatigue SF-8a and MFSAF TSS-7, were also achieved with statistical significance.
Safety and Tolerability
Rusfertide was generally well-tolerated in the Phase 3 VERIFY trial, with a safety profile consistent with previous clinical studies. The majority of adverse events were grade 1-2 injection site reactions, and all serious adverse events reported were deemed unrelated to the drug. Importantly, there was no evidence of an increased risk of cancer in rusfertide-treated patients compared to those on placebo.
Clinical Significance
Polycythemia vera is a rare blood cancer characterized by an overproduction of red blood cells, leading to increased blood viscosity and a higher risk of cardiovascular and thrombotic events. Many PV patients require regular phlebotomies to manage elevated hematocrit levels, which can be burdensome and exacerbate symptoms such as fatigue, visual disturbances, and iron deficiency.
"The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist.
Next Steps
Protagonist and Takeda plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. The companies also intend to submit their findings to regulatory agencies, seeking potential approval for rusfertide as a new treatment option for polycythemia vera.
