Tag Archives: rusfertide

Rusfertide Reduces Phlebotomy Need, Improves Symptom Control in Polycythemia Vera

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November 21, 2024

Author(s): Alexandra Gerlach, Associate Editor

Rusfertide (Takeda; Protagonist Therapeutics Inc) controlled erythrocytosis, maintained a hematocrit of less than 45% and reduced or eliminated the use of phlebotomy in patients with polycythemia vera (PV), according to data from the REVIVE trial (NCT04057040). Published in The New England Journal of Medicine, the results suggest the agent could become an additional therapeutic tool to reduce disease-related symptoms and the need for phlebotomy.1,2

Blood cells | Image Credit: © Ifti Digital – stock.adobe.com

PV is a rare type of blood cancer characterized by the overproduction of red blood cells in the bone marrow, contributing to blood clots, as well as the development of other blood disorders, such as myelofibrosis (MF). Both PV and MF are types of BCR‐ABL1‐negative myeloproliferative neoplasms with shared mutations and are associated with risk of thrombosis, hemorrhagic complications, and progression to acute myeloid leukemia. Approximately 1 in 4 patients with PV will develop MF, which is referred to as post–polycythemia vera myelofibrosis.3-5

Standard-of-care treatment for PV focuses on symptom reduction including treatments for to reduce itching or control blood cell counts, using agents such as hydroxyurea (Droxia; Bristol Myers Squibb) or ruxolitinib (Jakafi; Incyte Corp). The most common treatment for PV is frequent blood withdrawals to decrease blood volume, which is done via phlebotomy.5

Rusfertideis is an injectable, peptide mimetic of hepcidin. Hepcidin, produced in the liver, is a master regulator of iron trafficking. Some preclinical models suggest that increasing hepcidin could help control red blood cell production in patients with PV. In the phase 2 REVIVE trial, rusfertide demonstrated favorable safety and efficacy, with the potential to greatly decrease or eliminate the need for phlebotomy.2

The international, phase 2 REVIVE trial is divided into 2 parts. In part 1, patients were enrolled in a 28-week dose-finding assessment of rusfertide. In part 2, a double-blind, randomized withdrawal period, patients were assigned 1:1 ratio to receive either rusfertide (n = 30) or placebo (n = 29) for 12 weeks. The primary end point was response, which was defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Outcomes were reported by patients and were assessed using the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).2

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Rusfertide Treatment Strengthens Response and Decreases Erythrocytosis Among Patients With Polycythemia Vera

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Jordan Kadish

03/22/2024

According to findings from the international phase 2 REVIVE trial published in The New England Journal of Medicine, treatment with rusfertide, a peptide mimetic of the master iron regulatory hormone hepcidin, strengthened responses and decreased erythrocytosis among patients with polycythemia vera (PV). Patients who received rusfertide demonstrated a mean hematocrit of less than 45% during the dose-finding period.

Marina Kremyanskaya, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, New York, and coauthors stated, “Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis,” or a high concentration of red blood cells in the blood. “The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown,” they added.

To expand on the available research, the study authors aimed to assess the efficacy of rusfertide among patients with polycythemia vera. The primary end point was a response, which was characterized by the hematocrit control, absence of phlebotomy, and finishing the trial regimen during part 2. The modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary was utilized to assess patient-reported outcomes of symptoms.

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Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera

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Marina Kremyanskaya, M.D., Ph.D., Andrew T. Kuykendall, M.D., Naveen Pemmaraju, M.D., Ellen K. Ritchie, M.D., Jason Gotlib, M.D., Aaron Gerds, M.D., Jeanne Palmer, M.D., Kristen Pettit, M.D., Uttam K. Nath, M.D., Abdulraheem Yacoub, M.D., Arturo Molina, M.D., Samuel R. Saks, M.D., et al., for the REVIVE Trial Investigators*

Abstract

BACKGROUND

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

METHODS

 

In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

RESULTS

Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P=0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

CONCLUSIONS

In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040. opens in new tab.)

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Rusfertide Improves Responses in Phlebotomy-Dependent Polycythemia Vera

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Caroline Seymour

Patients with phlebotomy-dependent polycythemia vera, a type of myeloproliferative neoplasm, treated with rusfertide experienced a response rate of 60% (n = 18/30) compared with 17% (n = 5/29) in those who received placebo (P = .002), according to updated findings from part 2 of the phase 2 REVIVE trial (NCT04057040) published in the New England Journal of Medicine.1

The international trial was designed with 3 parts: a 28-week, open-label, dose-finding portion in which rusfertide was added to a patient’s ongoing therapy of phlebotomy alone or cytoreductive therapy with optional phlebotomy; a double-blind, randomized withdrawal portion wherein patients were randomly assigned to receive rusfertide or placebo for 12 weeks (weeks 29 to 41); and an open-label extension period following patients on rusfertide therapy for up to 3 years.

Findings from part 1 showed that the estimated mean number of annual phlebotomies was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). Moreover, the mean maximum hematocrit level was 44.5±2.2% during part 1 vs 50.0±5.8% during the 28 weeks before the first dose of rusfertide. Patient quality of life was also improved on rusfertide, with a lower severity of disease-related symptoms.

“Rusfertide appears to represent a significant step forward in treating [patients with] polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” Marina Kremyanskaya, MD, PhD, an associate professor of medicine (hematology and medical oncology) at Icahn School of Medicine at Mount Sinai in New York, New York, and lead author of the study, stated in a news release.2 “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease which many patients and their physicians struggle to bring under control.”

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Rusfertide More Than Triples Responses Vs Placebo in Phlebotomy-Dependent Polycythemia Vera

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Caroline Seymour

Treatment with rusfertide led to a 60% response rate (n = 18/30) vs 17% (n = 5/29) with placebo in patients with phlebotomy-dependent polycythemia vera (P = .002), according to updated findings from part 2 of the phase 2 REVIVE trial (NCT04057040) which were published in the New England Journal of Medicine.1

The international trial was designed with 3 parts: a 28-week, open-label, dose-finding portion in which rusfertide was added to a patient’s ongoing therapy of phlebotomy alone or cytoreductive therapy with optional phlebotomy; a double-blind, randomized withdrawal portion wherein patients were randomly assigned to receive rusfertide or placebo for 12 weeks (weeks 29 to 41); and an open-label extension period following patients on rusfertide therapy for up to 3 years.

Findings from part 1 showed that the estimated mean number of annual phlebotomies was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). Moreover, the mean maximum hematocrit level was 44.5±2.2% during part 1 vs 50.0±5.8% during the 28 weeks before the first dose of rusfertide. Patient quality of life was also improved on rusfertide, with a lower severity of disease-related symptoms.

“Rusfertide appears to represent a significant step forward in treating [patients with] polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” Marina Kremyanskaya, MD, PhD, an associate professor of medicine (hematology and medical oncology) at Icahn School of Medicine at Mount Sinai in New York, New York, and lead author of the study, stated in a news release.2 “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease which many patients and their physicians struggle to bring under control.”

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Study shows early success of a novel drug in treating a rare and chronic blood cancer

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February 21, 2024

by The Mount Sinai Hospital

A novel treatment for polycythemia vera, a potentially fatal blood cancer, demonstrated the ability to control overproduction of red blood cells, the hallmark of this malignancy and many of its debilitating symptoms in a multi-center clinical trial led by the Icahn School of Medicine at Mount Sinai.

In the phase 2 study, the drug rusfertide limited excess production of red blood cells, the main manifestation of polycythemia vera, over the 28-week course of treatment. The results suggest it could replace therapeutic phlebotomy, a common form of treatment which has proven to be a burden for many patients. The results of the study were published today (Feb. 21) in The New England Journal of Medicine.

“Rusfertide appears to represent a significant step forward in treating polycythemia vera through 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.

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