FDA Grants Priority Review to Rusfertide for Polycythemia Vera

The U.S. Food and Drug Administration (FDA) has accepted the new drug application for rusfertide (PTG-300) and granted it priority review for the treatment of adults with polycythemia vera (PV), according to a news release from Takeda and Protagonist Therapeutics. Rusfertide is an investigational, first-in-class hepcidin mimetic peptide designed to help control elevated red blood cell levels in PV.

“There is an urgent need for innovative treatment options in polycythemia vera, where patients currently face limited therapeutic choices to control their hematocrit and significant symptom burden,” said Dr. Andy Plump, president of R&D at Takeda. “The FDA's acceptance of our new drug application brings us closer to potentially offering a first-in-class therapy that could meaningfully improve clinical outcomes and quality of life. This milestone is a reflection of our successful partnership with Protagonist and Takeda’s unwavering commitment to advancing innovative treatments in hematologic cancers where significant unmet needs persist.”

The FDA’s decision to grant priority review shortens the standard review timeline and signals that the agency considers the therapy a potential significant improvement over available treatments. A regulatory decision is expected in the third quarter of this year. In addition to priority review, rusfertide has received breakthrough therapy, orphan drug and fast track designations.

What is rusfertide and how could it help patients with PV?

Rusfertide is a once-weekly, self-administered injection designed to mimic hepcidin, a natural hormone that regulates iron levels and red blood cell production. In polycythemia vera, the body produces too many red blood cells. This leads to thickened blood, increasing the risk of serious complications such as stroke, deep vein thrombosis and pulmonary embolism.

The primary goal of treatment in PV is to maintain hematocrit (the percentage of red blood cells in the blood) below 45%. When hematocrit rises above that level, patients often require phlebotomy, a procedure that removes blood from the body to reduce red blood cell counts. Many patients require frequent phlebotomies, which can be burdensome and disruptive to daily life.

In clinical studies, adding rusfertide to standard treatment improved hematocrit control, reduced the need for phlebotomy and improved patient-reported symptoms, including fatigue. Investigators reported that rusfertide was generally well tolerated through 52 weeks of treatment. The most common side effects were injection site reactions, anemia and fatigue, most of which were mild to moderate. Serious side effects occurred in a small proportion of patients.

Phase 3 VERIFY trial results support FDA filing

The new drug application is primarily supported by results from the phase 3 VERIFY study, a global, randomized, placebo-controlled trial that enrolled 293 patients with PV. Participants had uncontrolled hematocrit levels and required ongoing phlebotomy despite receiving standard treatment, which could include phlebotomy, hydroxyurea, interferon or ruxolitinib.

The study evaluated once-weekly rusfertide plus standard of care compared with placebo plus standard treatment. The primary endpoint measured how many patients avoided meeting criteria for phlebotomy eligibility between weeks 20 and 32. Phlebotomy eligibility was defined as hematocrit levels reaching at least 45% and rising significantly from baseline, or reaching 48% or higher.
Rusfertide met the primary endpoint and all four key secondary endpoints. Patients receiving rusfertide were more likely to maintain controlled hematocrit levels and experienced fewer phlebotomies compared with those receiving placebo. Improvements were also observed in patient-reported fatigue and symptom burden.

All patients have completed the randomized portion of VERIFY and are continuing in the open-label extension phase.

Long-term data from REVIVE and THRIVE

Additional support for the filing comes from the phase 2 REVIVE study and its long-term extension study, THRIVE. REVIVE evaluated rusfertide across multiple study phases, including dose-finding, randomized withdrawal and open-label expansion components.

THRIVE continues to assess long-term durability of response and safety in patients who previously participated in REVIVE and completed at least 12 months of treatment. The extension study is designed to evaluate whether patients can maintain hematocrit control and reduced phlebotomy requirements over an additional two-year period.

Understanding polycythemia vera and the unmet need

Polycythemia vera is a chronic blood cancer characterized by overproduction of red blood cells. Elevated blood thickness increases the risk of life-threatening blood clots. Patients frequently experience symptoms such as severe fatigue, itching, night sweats and difficulty concentrating.

Current treatment strategies focus on reducing clot risk and controlling hematocrit. Although therapies such as hydroxyurea, interferon and ruxolitinib are available, many patients continue to require repeated phlebotomy and experience ongoing symptom burden.

If approved, rusfertide would represent a first-in-class therapy that directly targets iron regulation and red blood cell production. For patients living with PV, this approach could offer more consistent hematocrit control and potentially reduce the physical and emotional toll associated with frequent procedures.

A final FDA decision is expected in the third quarter of this year.