FDA Application Submitted for Rusfertide Treatment in Polycythemia Vera

Takeda and Protagonist Therapeutics have announced the submission of a new drug application to the U.S. Food and Drug Administration (FDA), seeking the approval of rusfertide for the treatment of adults with polycythemia vera. This regulatory milestone aims to provide a new therapeutic option for patients living with this chronic blood disorder characterized by the overproduction of red blood cells, a condition which falls under the banner of myeloproliferative neoplasms, or MPNs.

Rusfertide is an investigational first-in-class hepcidin mimetic peptide administered through a subcutaneous injection, designed to regulate iron homeostasis and red blood cell production to help patients maintain control of their hematocrit levels.

The application for approval is supported by data from the phase 3 global, randomized, placebo-controlled VERIFY study and the phase 2 REVIVE study. In the VERIFY study, researchers conducted a 32-week primary analysis and reported 52-week results showing that the trial met its primary endpoint and all four key secondary endpoints. Patients with polycythemia vera who received rusfertide in addition to their standard of care therapy demonstrated a substantially higher response rate when compared to those who received a placebo plus standard of care.

The clinical findings highlighted several benefits for patients, including durable control of hematocrit levels. Maintaining hematocrit at less than 45% is a primary goal in the management of polycythemia vera to help prevent life-threatening events such as stroke, deep vein thrombosis and pulmonary embolism. The study data also showed that treatment with rusfertide led to a reduction in the requirements for phlebotomy, a procedure used to remove excess blood from the body. Additionally, patients reported improvements in pre-specified patient reported outcome endpoints, which measure the burden of symptoms such as severe fatigue, night sweats, pruritus and difficulty concentrating.

Based on its potential to offer a substantial improvement over currently available therapies, the FDA has granted rusfertide breakthrough therapy designation. The drug has also received orphan drug designation and fast track designation to expedite its development and review.

Rusfertide Trial details

The phase 3 VERIFY study is an ongoing, three-part investigation involving 293 patients with polycythemia vera. Participants in the study were characterized as being phlebotomy-dependent and having uncontrolled hematocrit despite receiving standard of care treatments, which could include hydroxyurea, interferon, Jakafi (ruxolitinib) or phlebotomy alone. The study is designed to evaluate the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide over a 156-week period.

The primary endpoint of the VERIFY study focused on the proportion of patients who achieved a response during weeks 20 to 32. A response was defined as the absence of "phlebotomy eligibility." In this trial, a patient was considered eligible for phlebotomy if they had a confirmed hematocrit of 48% or higher, or a confirmed hematocrit of 45% or higher that was at least 3% higher than their original baseline value. While all patients have completed the randomized, placebo-controlled portion of the trial, they have now transitioned into open-label portions of the study. An extension is also available for participants who continue to derive benefit from the treatment beyond the initial 156 weeks.

Supporting evidence also comes from the phase 2 REVIVE study, which included a 28-week dose-finding part with 70 patients, a 13-week randomized withdrawal part with 59 patients and a 52-week open-label expansion with 58 patients. Furthermore, an ongoing open-label extension study known as THRIVE is evaluating 46 patients who previously participated in REVIVE. The THRIVE study is designed to assess the long-term maintenance of hematocrit control and the safety of the medication over an additional two-year treatment period.

Understanding the Safety of Rusfertide

According to the clinical trial data released by the companies, rusfertide has been generally well-tolerated in studies conducted to date. Because it mimics the action of hepcidin — a natural hormone in the body — the medication targets the underlying mechanism of iron dysregulation to reduce excess red blood cell production.

The safety profile is being further monitored in the ongoing THRIVE and VERIFY studies. In the VERIFY study, the safety of once-weekly subcutaneous self-injection was compared against a placebo, with both groups continuing their standard of care. Long-term durability of the safety profile remains a key focus of the ongoing two-year THRIVE extension for patients who have already completed at least 12 months of therapy.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

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