FDA approves hepcidin-mimicking peptide rusfertide for polycythemia vera

What changed

The Food and Drug Administration on August 28 approved Mimrylo, or rusfertide, to treat erythrocytosis in adults with polycythemia vera. It is the first FDA-approved treatment for the disease that mimics hepcidin, the hormone that regulates how iron moves through the body.

Polycythemia vera is a chronic myeloproliferative blood cancer in which excessive red-cell production raises hematocrit, the proportion of blood occupied by red cells. The resulting increase in blood viscosity is associated with clots, stroke and heart attack. Treatment commonly includes phlebotomy—removing blood to lower hematocrit—and, for some patients, drugs that suppress blood-cell production.

Rusfertide adds a different mechanism. The injectable peptide restricts the iron available for erythropoiesis, reducing the raw material used to make new red cells. FDA approved it specifically for erythrocytosis in adults with polycythemia vera, not as a cure for the underlying cancer.

The phase 3 evidence

The approval was supported by VERIFY, a multicenter, randomized, double-blind, placebo-controlled phase 3 trial. Investigators enrolled 293 adults who continued to require frequent phlebotomy despite standard care. Participants were assigned equally to rusfertide or placebo for 32 weeks while continuing their existing treatment; about 56% in each group were also receiving cytoreductive therapy.

The primary endpoint was clinical response from weeks 20 through 32, defined by avoiding laboratory criteria that would make a participant eligible for phlebotomy. That endpoint was reached by 76.9% of participants assigned rusfertide and 32.9% assigned placebo.

Across the full 32-week period, participants received an average of 0.5 phlebotomies with rusfertide versus 1.8 with placebo. Investigators also reported that 62.6% of the rusfertide group maintained hematocrit below 45%, compared with 14.4% of the placebo group. Patient-reported fatigue and symptom measures favored rusfertide, although those outcomes were secondary to hematocrit and phlebotomy control.

Earlier support came from the randomized-withdrawal portion of the phase 2 REVIVE trial, published in 2024. That study found that switching participants from rusfertide to placebo was associated with a loss of response, helping establish that hematocrit control was attributable to the drug rather than simply continued observation.

Safety and monitoring remain consequential

In the controlled phase of VERIFY, injection-site reactions occurred in approximately 56% of rusfertide recipients and 33% of placebo recipients. Anemia occurred in about 16% and 4%, respectively. The prescribing safety information also warns about new or worsening thrombocytosis, or elevated platelet counts, as well as injection-site reactions and potential fetal harm.

Those risks are particularly relevant because the drug deliberately changes iron availability and blood-cell production. Approval therefore does not turn hematocrit management into a self-directed treatment decision; laboratory monitoring and adjustment within hematology care remain part of its clinical use.

What the approval does not establish

VERIFY provides strong evidence that rusfertide can reduce phlebotomy burden and improve hematocrit control in the studied population. Its placebo-controlled period lasted 32 weeks, however, and the primary endpoint was not a reduction in strokes, blood clots, cardiovascular deaths, progression to myelofibrosis or overall mortality.

Maintaining hematocrit below 45% is an established treatment goal, but the trial was not designed to prove that rusfertide itself prevents those longer-term outcomes. The study’s open-label extension is continuing, so durability and uncommon adverse effects require further follow-up. Generalizability is also clearest for adults who, like the trial participants, needed repeated phlebotomy despite ongoing standard care.

The practical change is narrower but important: clinicians now have an approved hepcidin-mimicking peptide that directly limits iron availability for red-cell production and substantially reduced phlebotomy eligibility over 32 weeks. Whether that control translates into better long-term clinical outcomes remains the central unanswered question.