Rusfertide-a New Option to Avoid Phlebotomy
Treatment with Rusfertide (PTG-300) may be a new option for patients with polycythemia vera (PV) requiring phlebotomy to remove excess blood cells. Study results presented during the European Hematology Association Virtual Congress suggest that Rusfertide reverses iron deficiency, improves disease-related symptoms, and eliminates the need for therapeutic phlebotomy.1 In June 2021, the FDA granted breakthrough therapy designation to rusfertide as a potential therapeutic option for patients with PV to reduce red blood cell production in those who do not require further treatment for thrombocytosis and/or leukocytosis.5
PV is characterized by the increased production of red blood cells (RBC) and a higher risk of blood clots (thrombosis). To reduce this risk PV patients are treated with periodic phlebotomy with or without cytoreductive therapy.2 Patients with PV also often have iron deficiency at the time of diagnosis and receiving several phlebotomies can worsen this condition.
About Rusfertide
Rusfertide is a hepcidin memeitc that works by suppressing blood cell production in PV by tricking the bone marrow into thinking it’s already iron deficient when it isn’t. This slows down the production of red blood cells keeping the hematocrit under 45%.
In the setting of PV hepcidin is low and ferroportin is open, thus allowing iron to freely flow into the plasma, making it available and resulting in uncontrolled erythropoiesis. In the presence of rusfertide, ferroportin is closed, and therefore, iron is not available to freely flow into the plasma which limits the amount of iron that is available for red blood cell production.
A phase 2 study enrolled patients with PV who had at least 3 phlebotomies with or without concurrent cytoreductive therapy in the 6 months prior to the trial. Rusfertide was subcutaneously administered on a weekly basis in addition to previous standard therapy. Rusfertide was well tolerated with minimal side effects. The data showed that when treated with rusfertide, a majority of patients were able to eliminate therapeutic phlebotomies, maintain a target hematocrit level of less than 45 percent, reverse iron deficiency, and experience symptom improvements.
“These results provide evidence that rusfertide may have clinical benefit for patients with polycythemia vera,” Ronald Hoffman, MD, the Albert A. and Vera G. List Professor of Medicine and director of the Myeloproliferative Disorders Research Program at Mount Sinai, stated in a press release on the data.4
Kadcyla (Trastuzumab Emtansine) in HER2-Positive Early Breast Cancer with Residual Invasive Disease
Long-term results demonstrate improved survival and sustained improvement in invasive disease-free survival for study patients treated with Kadcyla vs Herceptin
Lumakras (Sotorasib) in combination with Vectibix (Panitumumab) FDA Approved for Metastatic Colorectal Cancer with KRAS G12C Mutation
CODEBreaK 300 study demonstrated combination more than doubled progression-free survival compared to physician’s choice of standard of care
“The rate of phlebotomies was very high in this heavily phlebotomy-dependent patient population prior to initiation of therapy. As soon as patients initiated treatment with rusfertide, the rate of phlebotomy decreased dramatically” said Marina Kremyanskaya, MD, PhD, lead study author and assistant professor of medicine, hematology, and oncology at Mount Sinai Hospital, in a presentation on the data. “Most of the patients who required phlebotomy during this period were in the dose-saturation phase of the trial and needed a higher dose.”
The REVIVE Clinical Trial
Data from the REVIVE clinical study were released in April 2023 and confirmed that rusfertide treatment results in a significant reduction in the need for therapeutic phlebotomy in phlebotomy-dependent patients. Ronald Hoffman, MD, the Albert A. and Vera G. List Professor of Medicine (Hematology and Oncology), director of the Myeloproliferative Research Program at the Icahn School of Medicine at Mount Sinai, and principal investigator of the study, said. “we now have further confirmation of rusfertide’s potential to serve as an important future treatment option for patients with PV.”
The REVIVE trial demonstrated rusfertide’s could both reduce phlebotomy requirements and improve PV related symptoms of fatigue, problems with concentration, inactivity, and itching.6
Protagonist Therapeutics announces highly statistically significant results from the randomized withdrawal portion of the REVIVE study of rusfertide in polycythemia vera.
Patients with PV who have hematocrit levels above 45% are at a greater risk of thrombosis. Standard therapy for these patients includes therapeutic phlebotomy alone or in combination with cytoreductive agents. However, current therapies are not effective in reducing hematocrit levels below 45% and are not all well tolerated.
References
- Kremyanskaya M, Ginzburg Y, Kuykendall A, et al. PTG-300 eliminates the need for therapeutic phlebotomy and reverses iron deficiency in both low and high-risk polycythemia vera patients. Presented at: European Hematology Association 2021 Virtual Congress; June 9-17, 2021; virtual. Abstract S200.
- Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. doi:10.1056/NEJMoa1208500
- Protagonist Therapeutics receives FDA breakthrough therapy designation for rusfertide in polycythemia vera. News release. Protagonist Therapeutics. June 3, 2021. Accessed June 12, 2021. https://bit.ly/3pMfKYO
- Protagonist Therapeutics announces updated phase 2 data supporting long-term efficacy of rusfertide in polycythemia vera. News release. Protagonist Therapeutics. June 11, 2021. Accessed June 11, 2021.
Protagonist Therapeutics receives FDA breakthrough therapy designation for rusfertide in polycythemia vera. News release. Protagonist Therapeutics. June 3, 2021. Accessed September 20, 2022. bit.ly/3R0Tir8
News release. Protagonist Therapeutics. March 15, 2023. Accessed April 3, 2023. https://www.yahoo.com/lifestyle/protagonist-therapeutics-announces-highly-statistically-113000427.html
