Protagonist's Rusfertide Approval Expands Options and Eases Burden in Polycythemia Vera
核心洞察
The FDA has approved rusfertide (Mimrylo (搜索)), a first-in-class hepcidin mimetic, for controlling hematocrit in adults with polycythemia vera (搜索).
In the phase 3 VERIFY trial, 76.9% of rusfertide-treated patients achieved clinical response versus 32.9% on placebo at 32 weeks.
Rusfertide is self-injected and can be combined with cytoreductive therapy, with injection-site reactions and anemia as the main adverse effects to monitor.
The FDA has approved rusfertide (Mimrylo (搜索)), a first-in-class hepcidin mimetic, for controlling hematocrit in adults with polycythemia vera (搜索) and reducing reliance on repeated phlebotomies. The approval was supported in part by the phase 3 VERIFY trial (NCT05210790), in which 32-week results from part 1a showed a clinical response rate of 76.9% with rusfertide (n = 147) versus 32.9% with placebo (n = 146; P < .0001).
VERIFY enrolled patients with polycythemia vera (搜索) and a phlebotomy requirement of three procedures in the prior six months or five over the prior year, regardless of cytoreductive therapy, risk status or prior treatment history. Patients continued their existing standard of care, including hydroxyurea, interferon or ruxolitinib (Jakafi), and were randomized to rusfertide or placebo after a dose-titration period of up to 20 weeks. The primary end point, absence of phlebotomy eligibility between weeks 20 and 32, favored rusfertide, as did key secondary end points covering phlebotomy numbers and phlebotomy-free status, along with patient-reported outcomes on the PROMIS fatigue score and the Myelofibrosis Symptom Assessment Form.
Rusfertide raises hepcidin levels, decreasing iron delivery to the bone marrow and restricting erythropoiesis to hold hematocrit below 45%, a threshold tied to cardiovascular and thrombotic risk. Clinicians should watch for injection-site reactions, which were mostly mild and manageable supportively, and for anemia during titration, with labs checked every two to four weeks until a stable dose is reached. Long-term data from the phase 2 REVIVE trial (NCT04057040) and the phase 3 THRIVE extension study (NCT06033586) show no new safety concerns over four to five years of treatment. Other hepcidin-targeting approaches in development include the antisense oligonucleotide sapablursen, small interfering RNAs and monoclonal antibodies.
Source: OncLive