by David Wallace

Key Points

---

What is Polycythemia Vera?

Polycythemia vera (PV) is a rare blood cancer that causes the body to make too many red blood cells, leading to thick, sticky blood that increases the risk of dangerous complications like stroke, deep vein thrombosis, and pulmonary embolism. People with PV experience burdensome symptoms, including severe fatigue and difficulty concentrating.

The current standard treatment involves regular phlebotomy sessions, removing blood from patients’ bodies to reduce the number of red blood cells. Many patients need these procedures every few weeks, which can be uncomfortable, time-consuming, and very disruptive to daily life. Some patients also take medications like hydroxyurea, interferon, or ruxolitinib, but these don’t eliminate the need for blood draws and can have significant side effects. Now, a promising new drug called rusfertide is offering hope for a better way to treat this challenging disease.

How Rusfertide Works

Rusfertide represents an entirely new approach to treating polycythemia vera. It’s called a “hepcidin mimetic,” which means it copies the action of hepcidin, a natural hormone that regulates iron in the body. Iron is essential for making red blood cells, so by controlling iron availability, rusfertide can reduce the overproduction of red blood cells that characterizes PV.

Unlike current treatment (phlebotomy) that simply removes excess red blood cells after their production, rusfertide works upstream to prevent the overproduction of these cells in the first place. Patients receive the drug as a weekly injection under the skin, similar to how people with diabetes inject insulin.

Breakthrough Trial Results

The Phase 3 VERIFY trial, which took place in several countries, compared rusfertide to a placebo in patients with polycythemia vera who still needed regular blood draws even after trying other treatments. The results were remarkable: 77% of patients treated with rusfertide achieved a clinical response compared to only 33% of those receiving placebo.

Clinical response in this study meant maintaining healthy hematocrit levels (the percentage of red blood cells in the blood) without needing phlebotomy. Rusfertide treatment was associated with maintaining hematocrit levels below 45% and significantly reduced or eliminated the use of phlebotomy. Some patients went extended periods without needing any blood draws at all.

The benefits went beyond just reducing phlebotomy needs. Patients also experienced decreased PV-related symptoms. Quality of life measurements showed meaningful improvements, addressing fatigue, brain fog, and other symptoms that significantly impact daily living for PV patients.

Safety Profile

Safety is always a primary concern with any new medication, especially for a chronic condition requiring long-term treatment. The VERIFY trial showed a favorable safety profile, with the majority of adverse events being grade 1 or 2 injection site reactions. All serious adverse events were deemed not related to the drug, and there was no evidence of increased cancer risk in rusfertide-treated patients.

Long-term follow-up data from earlier studies showed that patients remained essentially phlebotomy-free while on rusfertide treatment, suggesting the benefits are sustained over time.

Looking Ahead

The success of the VERIFY trial represents a major milestone for polycythemia vera patients who have had limited treatment options for decades. Plans are underway to seek regulatory approval for the treatment of PV in the United States, Europe, Japan, and other regions.

The drug is being developed through a collaboration between Protagonist Therapeutics and Takeda, two pharmaceutical companies working together to bring this treatment to patients worldwide. If approved, rusfertide could transform the treatment landscape for PV, potentially allowing patients to manage their condition with weekly injections instead of frequent blood draws.

For the thousands of people living with polycythemia vera, rusfertide represents hope for a more convenient, effective treatment that could significantly improve their quality of life while providing better disease control.