Protagonist Therapeutics and Takeda have disclosed that their Phase 3 VERIFY trial for rusfertide in polycythemia vera (PV) patients has achieved its primary endpoint.
The late-stage study revealed a significantly larger proportion of clinical responders among those administered rusfertide compared to the placebo group.
Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic. It has received both orphan drug designation and fast track designation from the US Food & Drug Administration (FDA), highlighting its potential significance in treating this rare blood disorder.
The VERIFY trial is a large-scale, global investigation assessing the efficacy and safety of rusfertide over 156 weeks in 293 patients dependent on phlebotomy.
Participants were randomly assigned to receive either rusfertide or a placebo alongside standard care treatments such as hydroxyurea, interferon, or ruxolitinib. The main objective was to determine the proportion of patients achieving a response between weeks 20 and 32, defined by the absence of phlebotomy eligibility.
The findings demonstrated that 77% of patients treated with rusfertide reached clinical response, compared to 33% in the placebo cohort. This outcome highlights the potential role of rusfertide as a treatment for PV patients who remain dependent on phlebotomy despite existing therapies.
In addition to meeting the primary endpoint, all four key secondary endpoints were also achieved. This includes the primary endpoint set by European Union regulators, which involved an average of 0.5 phlebotomies per patient in the rusfertide arm versus 1.8 in the placebo arm over weeks 0-32.
Other secondary measures such as hematocrit control and patient-reported outcomes using PROMIS Fatigue SF-8a and MFSAF TSS-7 were also met with statistical significance.
Protagonist Therapeutics chief medical officer Arturo Molina said: “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 haematocrit control despite standard of care treatments.”
Safety data from the trial indicated that rusfertide was generally well tolerated, with adverse events primarily being mild to moderate injection site reactions.
No new safety issues were identified, and serious adverse events were not attributed to the drug. There was also no observed increase in cancer risk for patients treated with rusfertide compared to those on placebo.
Under their collaboration agreement signed in early 2024, Protagonist Therapeutics will receive a $25m milestone payment from Takeda following these positive results. This payment is contingent upon the completion of the VERIFY clinical study report.
