Protagonist Therapeutics Reports Positive Results in PV

Rare Daily Staff

Protagonist Therapeutics reported positive topline results from the blinded, placebo-controlled, randomized withdrawal portion of REVIVE, a study evaluating its experimental therapy rusfertide to treat patients with polycythemia vera.

Polycythemia vera is a rare myeloproliferative disease characterized by the excessive production of red blood cells. Well-established treatment guidelines focus on maintaining hematocrit levels continuously below 45 percent to reduce the risk of thrombotic events, but treatments are unable to maintain hematocrit to below the 45 percent target for many patients and may be associated with serious side effects.

Rusfertide is an experimental, injectable synthetic mimetic of the natural hormone hepcidin that regulates iron homeostasis and controls the absorption, storage, and distribution of iron in the body. The REVIVE study is now complete, with an open-label extension underway. The global phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing.

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 (69.2 percent versus 18.5 percent). 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 percent patients phlebotomy free in the rusfertide arm.

In patients with moderate or severe Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF) 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.

“The new randomized withdrawal data confirm our previous efficacy and safety findings of rusfertide in PV and support our strong conviction that rusfertide can be a potentially transformational therapeutic option for polycythemia vera,” said Dinesh Patel, president and CEO of Protagonist. “With the completion of the REVIVE study, the company’s topmost priority continues to be execution of the 250-patient global, pivotal, phase 3 VERIFY study in PV. The Protagonist team continues to work with full dedication alongside investigators, site staff and other partners with the shared aim of bringing this important potential therapy to PV patients.”

Photo: Dinesh Patel, president and CEO of Protagonist