Protagonist Therapeutics announces results from withdrawal portion of REVIVE

Protagonist Therapeutics announced topline results from the blinded, placebo-controlled, randomized withdrawal portion of REVIVE, a study evaluating rusfertide, a subcutaneous injectable hepcidin mimetic, in patients with polycythemia vera. Subjects receiving rusfertide achieved highly statistically significant improvements versus placebo in the primary endpoint. The double-blind, placebo-controlled, 12-week randomized withdrawal phase was included as Part 2 of the REVIVE study to evaluate rusfertide in PV patients with frequent phlebotomy requirements. In the trial, study subjects were initially enrolled in the 28-week open label dose-titration and efficacy evaluation Part 1 of the study, followed by 1:1 randomization of 53 subjects to placebo versus rusfertide therapy for a subsequent duration of 12 weeks. More subjects receiving rusfertide during the blinded randomized withdrawal portion of the REVIVE study were responders compared with placebo. A study subject was defined as a responder if the subject completed 12 weeks of double-blind treatment while maintaining hematocrit control without phlebotomy eligibility and without phlebotomy. During the 12 weeks of the blinded randomized withdrawal, only 2 of 26 subjects on rusfertide were phlebotomized, keeping 92.3% patients phlebotomy free in the rusfertide arm. In patients with moderate or severe Myeloproliferative Neoplasm-Symptom Assessment Form symptom scores at baseline, the change from baseline was statistically significant in fatigue, problems with concentration, inactivity and itching during the 28-week open label Part 1 of the study. Meaningful comparison of symptom assessments in Part 2 are not possible since a majority of subjects randomized to placebo discontinued prior to the 12-week assessment of MPN-SAF symptoms. Rusfertide was well tolerated, with localized injection site reactions comprising the majority of reported adverse events. No new safety signals were observed in these data following presentation of safety data from the REVIVE study at the American Society of Hematology December 2022 Annual Meeting.