Dr Kremyanskaya on the Efficacy of Rusfertide in Phlebotomy-Dependent Polycythemia Vera

Marina Kremyanskaya, MD, PhD, assistant professor of medicine, hematology, and medical oncology, Icahn School of Medicine, Mount Sinai, medical director, Inpatient Oncology Unit, The Mount Sinai Hospital, discusses key efficacy data for rusfertide (PTG-300) in the phase 2 REVIVE trial (NCT04057040) of phlebotomy-dependent polycythemia vera.

Polycythemia vera is a specific type of erythrocytosis that also features systemic symptoms and a high risk of thromboembolic and/or cardiovascular (CV) complications. High levels of the iron-regulator hepcidin have been implicated in uncontrolled red blood cell formation.

The REVIVE trial compared the ability of the first-in-class hepcidin mimetic rusfertide vs placebo to control erythrocytosis in patients with polycythemia vera who had previously received 3 or more phlebotomies in 28 weeks with or without concurrent cytoreductive therapy. The trial was composed of a dose-finding stage (part 1), blinded randomized withdrawal (part 2), and an open-label extension portion (part 3).

Patients in part 1 received a weekly subcutaneous dose of rusfertide that was individually adjusted to achieve a hematocrit level below 45% (range, 10 mg-120 mg). In part 2, patients were randomized to continue rusfertide or to receive placebo. The study's primary end point was efficacy as characterized by the proportion of responders in part 2, Kremyanskaya says. Responses were achieved if patients had a hematocrit level below 45% without phlebotomy eligibility, did not receive therapeutic phlebotomy, and had completed 12 weeks of treatment, she explains.

Results from the randomized withdrawal phase were presented at the 2023 EHA Congress and demonstrated that rusfertide produced a significantly higher percentage of responders vs placebo, Kremyanskaya reports. These percentages were 69.2% (n = 18/26) with rusfertide vs 18.5% (n = 5/27) with placebo. Additionally, most patients on the study had low ferretin levels at baseline, indicating iron deficiency, Kremyanskaya states. After treatment with rusfertide, ferretin levels were normalized and maintained for many of these patients, she says.

Analysis of symptom improvement was based on data from part 1, as the majority of patients in the placebo arm of part 2 discontinued treatment prior to the 12-week mark, Kremyanskaya continues. Rusfertide treatment significantly improved the rate and severity of problems with concentration, itching, fatigue, and inactivity, which tend to be moderate or severe at baseline. Regarding safety, the agent was generally well tolerated, Kremyanskaya concludes.

Disclosures: Dr Kremyanskaya reported receiving honoraria and being on the advisory board for Protagonist Therapeutics, Inc.