In a recent analysis, rusfertide appeared to show robust activity in combination with standard therapies in treating polycythemia vera (PV) in patients with suboptimal erythrocytosis control. Results of this analysis were presented at the 2022 ASCO Annual Meeting by Ronald Hoffman, MD, of Mount Sinai Hospital in New York, New York, and colleagues.
PV is marked by excessive erythrocytosis, and it is linked to greater risks of morbidity and mortality related to thrombotic events in the setting of poorly controlled hematocrit levels of below 45%, Dr Hoffman explained in his presentation. He also explained that existing therapies emphasize phlebotomy with or without cytoreductive agents. However, these are not always effective or tolerated. The research team evaluated the use of rusfertide, a hepcidin mimic, in patients with PV for treatment of erythrocytosis.
The study included results from two phase 2 trials involving patients with PV. In the first study, the REVIVE trial (ClinicalTrials.gov Identifier: NCT04057040), patients had a starting hematocrit level below 45% after treatment with phlebotomy, and they received rusfertide over a 28-week dose-finding phase, with an open-label extension phase that involved treatment to maintain hematocrit less than 45%. In the second trial, the PACIFIC trial (ClinicalTrials.gov Identifier: NCT04767802), patients with PV had hematocrit greater than 48%, and they were given rusfertide at 40 mg twice per week, then once weekly after hematocrit was less than 45%.
In the REVIVE trial, 70 patients were included, and phlebotomy alone had been the prior treatment for 48.6% of these patients, with a median of 34 days between phlebotomies. Over the first 28 weeks on treatment, 84% of patients in this trial did not require a phlebotomy. With rusfertide, red blood cell counts were also reduced, and no clinically significant changes were seen with platelet or white blood cell counts. Iron stores, based on ferritin measurements, were also considered restored with rusfertide. Symptom burden related to difficulties with concentration, were also improved by week 28, compared with baseline. Furthermore, a temporary suspension of rusfertide treatment due to a clinical hold was associated with worsening of hematocrit control.
The PACIFIC trial enrolled 20 patients. In this trial, Dr Hoffman and colleagues showed results demonstrating a rapid reduction in hematocrit upon treatment with rusfertide in this population, in addition to a rapid reduction in red blood cell counts.
Rusfertide appeared to be well tolerated in these trials. Most treatment-related adverse events were reported to be grade 1 or 2. Injection-side reactions were the most common such adverse event, and these were reported to be linked to 33% of injections in a safety analysis including both trials.
Dr Hoffman concluded that rusfertide induction given 2 times per week was effective at helping patients reach a target hematocrit level of less than 45% and without the need for phlebotomies. He also indicated rusfertide is being evaluated in a phase 3 trial that is currently enrolling patients (ClinicalTrials.gov Identifier: NCT05210790).
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
- Hoffman R, Ginzburg Y, Kremyanskaya M, et al. Rusftertide (PTG-300) treatment in phlebotomy-dependent polycythemia vera patients. Presented at ASCO 2022; June 3-7, 2022. Abstract 7003.