Study shows early success of new drug in treating rare, chronic blood cancer

A new treatment for polycythemia vera, a potentially fatal blood cancer, has been shown to control the overproduction of red blood cells, a hallmark of this malignancy and many of its debilitating symptoms, in a multicenter clinical trial led by the Icahn School of Medicine at Mount Sinai.

In the phase 2 study, the drug rusfertide limited excessive production of red blood cells, the main manifestation of polycythemia vera, during 28 weeks of treatment. The results suggest this could replace therapeutic phlebotomy, a common form of treatment that has proven to be a burden for many patients. The study results were published today (February 21) in The New England Journal of Medicine.

“Rusfertide appears to represent a significant advance in the treatment of polycythemia vera due to its unique approach of limiting the amount of iron available for blood cell production,” says Marina Kremyanskaya, MD, Ph.D., associate professor of medicine. (hematology and medical oncology). ) at Icahn Mount Sinai and lead author of the study.

Dr. Kremyanskaya, who is medical director of the inpatient oncology service at Mount Sinai Hospital, has conducted cutting-edge research on myeloid blood cancers. “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease that many patients and their doctors struggle to control,” she says.

“This groundbreaking work would not have been possible without my Mount Sinai co-investigators, Ronald Hoffman, MD, and Yelena Ginzburg, MD. Thanks to their close collaboration, we were able to move laboratory results from the bench to the bedside,” says Dr. Kremyanskaya.

Dr. Hoffman is Professor of Medicine (Hematology and Medical Oncology) at Icahn Mount Sinai, lead author of the publication, and a leading researcher and clinician in the field of myeloproliferative neoplasms. Dr. Ginzburg, professor of medicine (hematology and medical oncology) at Icahn Mount Sinai, is an expert on iron metabolism; his fundamental scientific work provided significant preclinical rationale for investigation.

Polycythemia vera is a rare type of chronic myeloproliferative neoplasm, with 1 to 3 new cases per 100,000 people diagnosed each year in the United States. This happens when the bone marrow overproduces blood cells, a condition also known as erythrocytosis, which can thicken the blood and increase the risk of heart attack, stroke, and other blood clots.

Current therapies include aspirin; medicines that can reduce red blood cells in the bloodstream, such as hydroxyurea, interferon and ruxolitinib; and phlebotomy, which involves drawing blood using a needle from a vein to reduce blood volume.

Frequent phlebotomies have proven costly for patients due to the need for prolonged doctor visits. They can also worsen iron deficiency symptoms that already affect many patients with polycythemia vera. In addition, patients are often intolerant or fearful of this therapeutic option.

Additionally, studies have shown that with currently available treatment options, many patients will often have hematocrits, the percentage of red blood cells in the blood, above the clinically safe level of 45%, putting these patients at risk for higher risk of complications.

The Mount Sinai-led REVIVE trial was conducted at 16 centers in the United States and India. The safety and effectiveness of Rusfertide were evaluated in 70 patients with phlebotomy-dependent polycythemia vera.

Researchers found that the agent was associated with improved and durable control of hematocrit levels below 45% during the 28-week dose discovery period, and was superior to placebo during the 12-week waiting period that followed. Patients with many symptoms such as pruritus (itchy skin), night sweats, difficulty concentrating, and fatigue also reported improvements after treatment with rusfertide, which was well tolerated.

Rusfertide is an injectable medication that patients can self-administer at home. It works in the body by mimicking hepcidin, a hormone produced by the liver that serves as the master regulator of iron trafficking. It blocks the export of iron to the blood in a dose-dependent manner, leading to functional iron deficiency and reduced red blood cell production.

“Rusfertide shows great promise in achieving sustained hematocrit control in patients with polycythemia vera. Equally important, it has reduced the need for repeat phlebotomies, with some patients remaining virtually procedure-free for more than two years and a half,” notes Dr. Kremyanskaya. .

A phase 3 clinical trial is currently underway at global sites, with Mount Sinai once again taking a lead role.