Rusfertide stabilizes haematocrit for 2.5 years in PCV

The hepcidin mimetic rusfertide provides long-term control of haematocrit (2.5 years) and reduces the use of phlebotomy among patients with polycythemia vera (PCV) in the phase II REVIVE study.

Response rate with rusfertide was 69.2 percent (defined as haematocrit <45 percent during 12 weeks of treatment without phlebotomy) compared with 18.5 percent with placebo. Additionally, 24 of 26 patients treated with rusfertide did not receive phlebotomy compared with 12 of 27 in the placebo arm. [ASH 2023, abstract 745]

The REVIVE trial consists of three parts.  Part 1 was a dose-finding and dose-evaluation phase. Dr Ellen Ritchie from the Weill Cornell Medical College at Cornell University, New York, US reported findings from part 2 of the trial, a blinded, randomized, withdrawal of treatment phase, at ASH 2023.

Part 3 will be an open-label extension (OLE) to evaluate rusfertide dosing, safety, and efficacy for up to 3 years.

Ritchie said the randomized portion of the study was designed to look for efficacy. “Half of the patients were randomly assigned to placebo; half continued with rusfertide from weeks 29–41. At week 42, patients were allowed to take part in the OLE study.

The trial met the primary endpoint – 18 of 26 patients achieved a stable haematocrit level of <45 percent. In the placebo arm of the withdrawal component, five of 27 patients achieved the primary endpoint. “Response to rusfertide was superior regardless of whether patients received cytoreductive therapy,” said Ritchie.

During the randomized withdrawal, 92.3 percent of those who continued with rusfertide did not require phlebotomy compared with 44.4 percent in the placebo arm. “Haemoglobin and erythrocyte counts increased only when rusfertide was held or discontinued,” she added.

Fifty-eight of the 70 patients enrolled in part 1 of the trial continued to part 3. As of mid-October, 57 patients had been treated for at least 1 year, 51 for ≥1.5 years, and 37 for ≥2 years.

“Mean haemoglobin levels generally remained stable and mean erythrocyte counts decreased through 2.5 years,” Ritchie reported. “Leukocyte counts also remained stable. Platelet count increased by about 30 percent as patients started rusfertide but did not increase further as they continued with treatment. Rusfertide resulted in normalization of serum ferritin levels over the 2.5 years.”

Patient-reported outcomes improved, including fatigue, early satiety, inactivity, concentration, night sweats, and itching.

Most adverse events were grade 1/2. Eight patients developed second malignancies.  Five high-risk patients had thromboembolic events.

When asked if the interval of treatment can be decreased, Ritchie said: “There is no data to support that. “Physicians were at liberty to adjust the dose to keep the haematocrit <45 percent. As this study cohort continues to be studied, that will be an interesting question: whether we can decrease the frequency or whether we can decrease the dose in some of these patients.”

PCV is a rare blood disorder characterized by excessive production of red blood cells, which can make the blood thicker. This can lead to increased blood viscosity, including thromboses.