New Hope for PV: Rusfertide Aims to End Phlebotomy Burden

OSAKA, Japan & NEWARK, Calif. – January 05, 2026 – A potential new era in the treatment of a rare, chronic blood cancer began today as Takeda and Protagonist Therapeutics announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for rusfertide. The investigational, first-in-class therapy is aimed at adults with polycythemia vera (PV), a condition that forces many to endure frequent and burdensome blood draws to manage their disease.

If approved, rusfertide would offer a novel approach to controlling the overproduction of red blood cells that characterizes PV. Administered as a once-weekly subcutaneous injection, the drug could significantly alter the treatment landscape for a patient population that has long sought more effective and less invasive options. The submission marks a major milestone in a decade-long development journey for the hepcidin mimetic peptide, which originated in Protagonist's labs.

A Potential Shift from Burdensome Procedures

For thousands of people living with polycythemia vera, life is dictated by their hematocrit levels. The disease, a type of myeloproliferative neoplasm, causes the bone marrow to produce too many red blood cells, thickening the blood and dramatically increasing the risk of life-threatening clots, strokes, and heart attacks. The primary goal of treatment is to keep hematocrit—the ratio of red blood cells to total blood volume—below 45%.

For many, the standard of care involves therapeutic phlebotomy, a procedure identical to blood donation, performed as often as every few weeks to manually remove excess red blood cells. While effective at lowering hematocrit, the process is burdensome, time-consuming, and can lead to iron deficiency, causing debilitating symptoms like severe fatigue and difficulty concentrating.

"This is an important milestone toward our goal of addressing critical gaps that patients living with polycythemia vera face today," said Teresa Bitetti, President of Takeda's Global Oncology Business Unit, in a statement.

The NDA submission is built on a foundation of strong clinical data from the Phase 3 VERIFY and Phase 2 REVIVE studies. The pivotal VERIFY trial showed that patients treated with rusfertide in addition to their standard therapy had a substantially higher response rate compared to those on placebo. Critically, rusfertide demonstrated the ability to provide durable hematocrit control, significantly reduce the need for phlebotomies, and improve patient-reported symptoms. This suggests a future where patients might be able to manage their condition with a simple self-injection at home, freeing them from the cycle of clinic visits and blood draws.

The Science of a 'Chemical Phlebotomy'

Rusfertide’s innovation lies in its unique mechanism of action, which has led experts to describe it as a "chemical phlebotomy." It mimics hepcidin, the body's master regulator of iron. In healthy individuals, hepcidin controls the amount of iron available in the bloodstream for red blood cell production. However, in most PV patients, hepcidin levels are abnormally low, allowing an unrestricted flow of iron to the bone marrow, which fuels the overproduction of red blood cells. This occurs even as the rest of the body becomes iron-deficient from repeated phlebotomies.

Rusfertide steps in to restore this crucial balance. By acting like hepcidin, it blocks iron from being released into the bloodstream from storage sites and from being absorbed in the gut. This starves the bone marrow of the excess iron it needs to create a dangerous surplus of red blood cells.

This approach is fundamentally different from existing cytoreductive therapies. Drugs like hydroxyurea or the JAK inhibitor ruxolitinib (Jakafi) work by suppressing bone marrow activity to slow cell production. While often effective, they can come with their own side effects and don't work for all patients. Rusfertide, by targeting the iron supply chain rather than the marrow "factory" itself, offers a non-cytoreductive strategy that directly addresses a core driver of the disease.

"Rusfertide has the potential to redefine the treatment paradigm for PV by offering patients a novel, first-in-class erythrocytosis-specific therapy that significantly reduces or eliminates the need for frequent phlebotomy," stated Dinesh V. Patel, Ph.D., President and CEO of Protagonist.

High Stakes in a Growing Market

The submission of rusfertide places Takeda and Protagonist at the forefront of innovation in a market poised for significant growth. The global market for polycythemia vera therapies, currently valued at approximately $2 billion, is projected by some analysts to exceed $5 billion by 2034, driven by an aging population and improved diagnostics.

Rusfertide will enter a competitive field that includes long-standing treatments like hydroxyurea and newer agents such as Incyte’s Jakafi and PharmaEssentia’s Besremi, a long-acting interferon. However, its unique mechanism and potential to eliminate phlebotomy for a large segment of patients could allow it to carve out a significant niche, particularly for those who are intolerant to or inadequately managed by current options.

The financial stakes are high for both companies. Under a worldwide collaboration agreement inked in early 2024, Protagonist received a $300 million upfront payment from Takeda. The deal includes a 50:50 profit-sharing arrangement in the U.S. market. However, the NDA submission triggers a 120-day window, after which Protagonist has the option to opt out of the profit-sharing agreement. Should it choose to do so, it would be eligible for up to $400 million in opt-out payments and significantly enhanced milestone payments and tiered royalties on global sales, shifting the commercial risk and reward structure heavily.

This strategic flexibility highlights the confidence both parties have in rusfertide's blockbuster potential. Takeda gains a promising late-stage asset to bolster its rare hematology franchise, while Protagonist, the drug's originator, stands to reap substantial financial rewards from its decade of scientific investment.

The journey for rusfertide is not yet over. The FDA has already granted the drug Breakthrough Therapy, Orphan Drug, and Fast Track designations, signaling its potential to offer a substantial improvement over available therapies and potentially expediting its path to market. With the application now officially under review, patients, physicians, and investors will be watching closely as regulators decide the fate of a drug that could fundamentally change what it means to live with polycythemia vera.