Rusfertide Earns Breakthrough Therapy Designation in Polycythemia Vera

The FDA granted rusfertide breakthrough therapy designation for patients with polycythemia vera.

An investigational drug called rusfertide may soon offer a new treatment option for people living with polycythemia vera, a rare blood cancer that causes the body to produce too many red blood cells. Protagonist Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted rusfertide breakthrough therapy designation, a step that could speed its path to approval.

This designation adds to rusfertide’s earlier orphan drug and fast track statuses, all of which provide regulatory advantages designed to help new therapies reach patients more quickly. In the news release, Protagonist said it plans to file a new drug application with the FDA in the fourth quarter of 2025.

Rusfertide is a first-in-class therapy that acts as a hepcidin-mimetic peptide. In polycythemia vera, high red blood cell counts lead to thickened blood, which increases the risk of blood clots, stroke and other serious complications. Standard care often includes medications such as hydroxyurea, interferon or ruxolitinib, along with regular phlebotomies (blood draws) to keep hematocrit levels under control. However, many patients continue to struggle with uncontrolled blood counts, treatment side effects, and disease-related fatigue.

By mimicking hepcidin, a natural hormone that regulates iron in the body, rusfertide helps reduce excess red blood cell production. In clinical trials, the therapy has shown the ability to control hematocrit levels, reduce the need for frequent phlebotomies and improve symptoms such as fatigue.

Positive Results from Phase 3 VERIFY Trial of Rusfertide in Polycythemia Vera

The FDA’s decision was supported by results from the global phase 3 VERIFY trial, which enrolled 293 patients with polycythemia vera. VERIFY is designed as a three-part, placebo-controlled study lasting 156 weeks, testing rusfertide in patients who remain dependent on phlebotomy despite standard treatment.

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, 32-week data from VERIFY were presented during a plenary session, underscoring the drug’s potential to change treatment practice.

According to the news release from Protagonist, patients who received rusfertide plus their current therapy achieved strong results across both primary and secondary trial end points. These included reliable hematocrit control, fewer phlebotomy procedures and meaningful improvements in patient-reported outcomes such as energy and fatigue levels.

“We are very pleased with the FDA’s decision, which highlights rusfertide’s potential to demonstrate substantial improvement over available therapies,” said Dr. Dinesh V. Patel, president and CEO of Protagonist Therapeutics, in the news release. “We remain on track to submit our NDA by the end of this year.”

Dr. Arturo Molina, chief medical officer at Protagonist, added in the news release, “The comprehensive data provide compelling evidence that rusfertide may help patients with polycythemia vera who cannot achieve adequate hematocrit control with standard treatments.”

FDA Designations and What They Mean for Rusfertide in Polycythemia Vera

Breakthrough therapy designation is granted to experimental treatments that show early evidence of providing a significant benefit over current options for serious conditions. It makes a therapy eligible for closer FDA guidance, faster development timelines and priority review.

Orphan Drug status, which rusfertide received in 2020, is given to medicines targeting rare diseases. It can provide additional benefits such as market exclusivity and tax incentives. Fast track designation helps speed the FDA review process. Together, these designations position rusfertide for an accelerated path toward potential approval.

All patients from the controlled portion of the VERIFY study have now moved into the open-label extension, where researchers are continuing to track long-term safety and efficacy.

If approved, rusfertide could become the first therapy of its kind for polycythemia vera. For patients who rely heavily on phlebotomy or struggle to maintain safe hematocrit levels on current drugs, rusfertide may represent a new option that directly targets the underlying biology of the disease.

References

1. “Rusfertide Receives Breakthrough Therapy Designation for Treatment of Erythrocytosis in Patients with Polycythemia Vera,” by Protagonist Therapeutics, Inc. News release; Aug. 25, 2025.
2. “Rusfertide Elicits Promising Responses in Polycythemia Vera,” by Alex Biese. CURE. News; March 3, 2025. https://www.curetoday.com/view/rusfertide-elicits-promising-responses-in-polycythemia-vera
3. “Rusfertide Reduces Phlebotomy Need, Improves Quality of Life in Polycythemia Vera,” by Ryan Scott. CURE. News; June 11, 2025. https://www.curetoday.com/view/rusfertide-reduces-phlebotomy-need-improves-quality-of-life-in-polycythemia-vera
4. “Expanding on a New Way to Manage Polycythemia Vera Without Iron Deficiency,” by Dr. Aaron Gerds. CURE. Video; June 10, 2025. https://www.curetoday.com/view/expanding-on-a-new-way-to-manage-polycythemia-vera-without-iron-deficiency

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