The US Food and Drug Administration (FDA) has approved Mimrylo (rusfertide) for adults with polycythemia vera (PV), a rare blood disorder that causes excessive production of red blood cells.

The approval of the hepcidin mimetic, developed by Protagonist Therapeutics and commercialised by Takeda, triggers $275 million in payments to Protagonist under the companies’ agreement.

The payment comprises a $200 million opt-out fee and a separate $75 million approval milestone. Protagonist is also eligible for up to a further $875 million in potential milestone payments, alongside tiered royalties of 14% to 29% on worldwide net sales.

Mimrylo is the first approved treatment for PV that mimics hepcidin, a hormone involved in regulating iron availability in the body. By limiting the amount of iron available for red blood cell production, the treatment is designed to help control haematocrit, the proportion of blood made up of red blood cells.

The FDA approval covers the treatment of erythrocytosis in adults with PV. Maintaining haematocrit below 45% is an important treatment goal because excessive red blood cell production can increase the risk of cardiovascular complications, including blood clots, stroke and heart attack.

The approval was supported by results from the Phase 3 VERIFY trial, a randomised, double-blind, placebo-controlled study involving 293 adults with PV who required frequent phlebotomies despite standard treatment.

During weeks 20 to 32, 76.9% of patients receiving Mimrylo achieved a response, defined by the absence of phlebotomy eligibility, compared with 32.9% of patients receiving placebo.

The trial also met four key secondary endpoints, including reductions in the number of phlebotomies, maintenance of haematocrit below 45% and improvement in fatigue measured using the PROMIS Fatigue Short Form 8a.

The most common adverse reactions were injection site reactions, reported in 56% of patients, and anaemia, reported in 16%.

Tanya Wroblewski, director of the Division of Nonmalignant Hematology within the FDA’s Center for Drug Evaluation and Research, said: “People living with polycythemia vera have long faced the challenge of managing a chronic blood disorder with frequent blood draws to help address the consequences of the red blood cell overproduction. Today’s approval of Mimrylo offers a new, first-in-class option that has the potential to meaningfully reduce patient burden.”

Protagonist discovered rusfertide and was responsible for its development through Phase 3 before Takeda assumed responsibility for regulatory submission and commercialisation following Protagonist’s decision to opt out of the programme in April 2026.

Dinesh Patel, president and chief executive officer of Protagonist Therapeutics, said: “Today’s FDA approval of MIMRYLO represents a paradigm shifting approach to management of PV. MIMRYLO mimics the action of hepcidin, the body’s natural master regulator of iron availability thereby controlling hematocrit levels and helping restore iron balance.

“MIMRYLO was conceived fourteen years ago with the idea that a mimetic of hepcidin, the body’s primary regulator of iron homeostasis, could address the underlying biology of erythrocytosis in PV. The approved label also reflects improvement in fatigue as measured by PROMIS Fatigue Short Form 8a.”

The approval gives patients with PV a new treatment approach aimed at controlling red blood cell production and reducing reliance on phlebotomy.