FDA Approves MIMRYLO (rusfertide), First-in-Class Hepcidin Mimetic for Polycythemia Vera
核心洞察
The U.S. FDA approved Takeda (搜索)'s MIMRYLO (搜索) (rusfertide), a first-in-class hepcidin mimetic, for treating erythrocytosis in adults with polycythemia vera (搜索) (PV), a blood cancer.
The approval is supported by the Phase 3 VERIFY trial, in which 76.9% of patients achieved clinical response during Weeks 20-32.
MIMRYLO (搜索) demonstrated hematocrit control, reduced phlebotomy burden, and improved fatigue, with injection site reactions and anemia as the most common adverse events.
Takeda (搜索) (TSE:4502/NYSE:TAK) announced U.S. Food and Drug Administration (FDA) approval of the New Drug Application (NDA) for MIMRYLO (搜索) (rusfertide) for the treatment of erythrocytosis in adults with polycythemia vera (搜索) (PV), a blood cancer. MIMRYLO is a first-in-class hepcidin mimetic designed to regulate iron distribution in the body and red blood cell overproduction to control hematocrit levels, which is the ratio of red blood cells to the total amount of blood in the body. Maintaining controlled hematocrit levels below 45% is the primary treatment goal in PV.
Uncontrolled Hematocrit Remains a Clinical Challenge
Affecting approximately 90,000 people in the U.S., PV is characterized by the overproduction of red blood cells (erythrocytosis), leading to elevated hematocrit which can increase blood viscosity, or thickness. This has the potential to result in life-threatening thrombotic events, including stroke, deep vein thrombosis and pulmonary embolism. Maintaining hematocrit levels consistently below 45% can prevent thrombotic events and alleviate burdensome symptoms, including severe fatigue, pruritus (itching), difficulty concentrating and night sweats.
An estimated 78% of patients still experience uncontrolled hematocrit with current standard of care, including phlebotomy and cytoreductive therapies. Patients with PV experiencing uncontrolled hematocrit have a four times higher risk of cardiovascular death or major cardiovascular events.
"For patients living with PV, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events," said Andrew T. Kuykendall, M.D., VERIFY lead investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "Current treatments, such as phlebotomy, leave a significant gap for too many patients and can pose challenges to daily life and routines. The approval of MIMRYLO (搜索) offers clinicians and patients a novel, first-in-class therapy that targets erythrocytosis, which drives excess red blood cell production in PV."
Phase 3 VERIFY Trial Supports Approval
The approval was supported by data from the global randomized Phase 3 VERIFY study (NCT05210790), an ongoing, three-part, global, randomized, placebo-controlled study evaluating MIMRYLO (搜索) in 293 patients with polycythemia vera (搜索) over a 156-week period. The study evaluated the efficacy and safety of once-weekly, subcutaneously self-administered MIMRYLO in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include phlebotomy, hydroxyurea, interferon and/or ruxolitinib.
MIMRYLO (搜索) met all efficacy endpoints and demonstrated a favorable safety profile. In the study, patients receiving MIMRYLO plus current standard of care demonstrated a higher response rate compared to placebo plus current standard of care, including hematocrit control, a reduction in the need for phlebotomy and improvement in fatigue as measured by PROMIS Fatigue Short Form 8a. The primary endpoint was the proportion of patients achieving a response during Weeks 20-32, defined as the absence of "phlebotomy eligibility," with 76.9% of patients achieving clinical response.
Key secondary endpoints evaluated at Week 32 included mean number of phlebotomies, proportion of patients maintaining hematocrit <45%, mean change in fatigue score as measured by PROMIS Fatigue Short Form 8a, and total symptom burden as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 4.0.
Safety Profile
MIMRYLO (搜索) was generally well-tolerated through 52 weeks of treatment in the VERIFY trial. The most common treatment-emergent adverse events in MIMRYLO-treated patients were injection site reactions and anemia. The most common (>15%) adverse reactions were injection site reactions (56%) and anemia (16%).
The prescribing information includes warnings and precautions for new or worsening thrombocytosis, injection site reactions (including Grade 3 reactions), and embryo-fetal toxicity. Because of the potential for serious adverse reactions in the breastfed child, including impaired iron absorption, patients are advised not to breastfeed during treatment with MIMRYLO (搜索) and for 30 days after the final treatment.
A New Treatment Paradigm
"People living with PV often experience complex and invisible symptoms, from extreme fatigue to the emotional strain of living with a chronic blood cancer," said Kapila Viges, Chief Executive Officer, MPN Research Foundation. "There remains a need for treatments that better address these daily challenges. This meaningful approval reflects important progress and brings forward a new treatment option in a disease where patients have long needed innovation and more choices."
MIMRYLO (搜索) is a first-in-class subcutaneous treatment that mimics the action of hepcidin, a natural hormone that regulates iron homeostasis and erythrocytosis. By targeting the underlying mechanism of iron dysregulation in polycythemia vera (搜索), MIMRYLO aims to reduce excess red blood cell production and help patients maintain hematocrit control. It is administered once weekly via subcutaneous injection.
"The approval of MIMRYLO (搜索) underscores the strength of Takeda (搜索)'s late-stage pipeline and our focus on developing genuinely differentiated therapies for patients who are urgently waiting for new options," said Julie Kim, President and Chief Executive Officer, Takeda.
Protagonist (搜索) discovered MIMRYLO (搜索) and led its development through Phase 3. Takeda (搜索) now has exclusive global development and commercialization rights for MIMRYLO. The open-label extension of the VERIFY trial is ongoing, and Takeda will share further findings at upcoming medical conferences. Takeda is also working with regulators outside of the U.S. to potentially bring MIMRYLO to more patients worldwide.