FDA Approves Takeda’s PV Therapy

Rare Daily Staff

The U.S. Food and Drug Administration has approved Takeda’s Mimrylo for adults with polycythemia vera, a rare blood cancer in which the bone marrow produces too many red blood cells.

The approval applies specifically to erythrocytosis, elevated red blood cell levels, in adults with PV. It provides a new way to manage a key driver of the disease and its complications.

Protagonist Therapeutics developed Mimrylo and licensed the drug to Takeda for worldwide commercialization. The approval triggers $275 million in payments to Protagonist under the companies’ collaboration agreement, including a $200 million opt-out fee and a $75 million approval milestone, the company said. Protagonist may also receive up to $875 million in additional milestone payments, as well as tiered royalties on worldwide sales. Takeda will commercialize Mimrylo globally.

Polycythemia vera, or PV, can make the blood thicker and more difficult to circulate. That raises the risk of serious complications, including blood clots, stroke and heart attack. Patients may also experience debilitating fatigue, itching, night sweats and difficulty concentrating. A central treatment goal is to keep hematocrit — the percentage of blood made up of red blood cells — below 45 percent, a level associated with lower cardiovascular risk.

For many patients, treatment has involved repeated phlebotomy, a procedure similar to donating blood that removes blood to lower the red blood cell count. Some patients also receive medicines intended to suppress blood-cell production. But people whose hematocrit remains uncontrolled may still need frequent blood draws, creating a persistent burden on daily life.

Mimrylo is a peptide designed to mimic hepcidin, the body’s chief regulator of iron availability. By limiting the iron available to produce new red blood cells, the treatment aims to reduce the overproduction that drives PV and help keep hematocrit under control. The medicine is self-administered once weekly as an injection under the skin.

“For patients living with PV, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events,” said Andrew Kuykendall, 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 offers clinicians and patients a novel, first-in-class therapy that targets erythrocytosis, which drives excess red blood cell production in PV.”

In the pivotal phase 3 VERIFY trial, which enrolled 293 adults with PV who needed frequent phlebotomies despite standard care, 76.9 percent of patients receiving Mimrylo did not require a phlebotomy during weeks 20 through 32 of the study. That compared with 32.9 percent of patients who received a placebo alongside standard care.

The study also found that patients taking Mimrylo required fewer phlebotomies overall and were more likely to maintain hematocrit below 45 percent. The Mimrylo group had a mean of 0.5 phlebotomies over 32 weeks, compared with 1.8 in the placebo group, according to reported trial results. Patients taking Mimrylo also reported improvement in fatigue measures.

The most common adverse reactions reported in prescribing information were injection-site reactions, affecting 56 percent of patients, and anemia, affecting 16 percent. Mimrylo can also increase platelet counts, and the label recommends regular complete blood count testing after treatment begins and during dose adjustments. The drug may cause fetal harm based on animal studies, and patients are advised to stop treatment if they become pregnant.