The US FDA has approved Mimrylo (rusfertide), the first hepcidin mimetic peptide cleared for polycythemia vera (PV), giving Takeda (NYSE: TAK) a first-in-class option for controlling erythrocytosis in adults with the rare blood cancer. The label covers treatment of erythrocytosis in adults with PV without restricting use to patients who have failed a prior therapy
Mimrylo is administered once weekly by subcutaneous self-injection. It acts as a hepcidin mimetic that regulates iron homeostasis and restricts iron availability for red blood cell production — an approach mechanistically distinct from the JAK inhibitors and interferons that currently dominate cytoreductive therapy in PV.
The approval was supported by the Phase III VERIFY trial (NCT05210790), a global, randomized, placebo-controlled study enrolling 293 adults with PV who had uncontrolled hematocrit despite current standard of care, including phlebotomy, hydroxyurea, interferon, and/or ruxolitinib. The primary endpoint — proportion of patients free of phlebotomy eligibility during Weeks 20–32 — was met, with 76.9% of patients in the Mimrylo arm achieving a clinical response. Key secondary endpoints at Week 32, including mean phlebotomy count, proportion maintaining hematocrit below 45%, and fatigue as measured by PROMIS Fatigue Short Form 8a, also favored Mimrylo. The most common adverse reactions were injection site reactions (56%) and anemia (16%); thrombocytosis monitoring is required after initiation and during dose changes.
Rusfertide was discovered by Newark, California-based Protagonist Therapeutics (Nasdaq: PTGX), which licensed worldwide rights to Takeda in January 2024 for an upfront payment of USD 300 million. Protagonist subsequently exercised its US opt-out right in April 2026, converting to a royalty and milestone structure. The April opt-out triggered an initial USD 200 million payment, while FDA approval triggered a further USD 275 million, comprising a USD 200 million opt-out payment and USD 75 million regulatory milestone. Protagonist is also eligible for tiered royalties of 14%–29% on worldwide net sales. A separate legacy interest in rusfertide was held by Zealand Pharma, which sold most of its 1% global sales royalty and associated milestones to Royalty Pharma for USD 100 million in August 2026, retaining a 0.25% royalty on annual sales above USD 1.5 billion.
Mimrylo enters a PV landscape where ruxolitinib — available as both the original Jakafi and, as recently approved, an extended-release formulation from Incyte Corporation — holds the established second-line cytoreductive position, and ropeginterferon alfa-2b-njft (Besremi, PharmaEssentia Corporation) carries a broad adult PV label. Mimrylo's iron-restriction mechanism, which targets erythrocytosis directly rather than the JAK-STAT pathway, differentiates it from both approved competitors. In addition, unlike ruxolitinib, whose PV indication is restricted to patients with inadequate response or intolerance to hydroxyurea, Mimrylo's label does not specify prior treatment failure. Takeda said it is pursuing regulatory submissions outside the US and that the open-label extension of VERIFY remains ongoing.
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