Rusfertide Administration Successful in Lowering Hematocrit Levels in Polycythemia Vera


In an interview with Targeted Oncology, Yelena Ginzburg, MD, discussed the research and use of rusfertide in patients with polycythemia vera.

Yelena Ginzburg, MD

Yelena Ginzburg, MD

Treatment with rusfertide in patients with polycythemia vera (PV) effectively achieved the target hematocrit without phlebotomy and was well-tolerated in patients, according to data presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition.

In a prior phase 2 trial, rusfertide demonstrated the ability to reduce the number of phlebotomies while sustaining a good hematocrit level of below 45% in patients with high-risk or low-risk PV. The randomized study population included individuals diagnosed with PV who had a baseline hematocrit above 48% and a history of 3 or more hematocrit values of above 48%.

Each subject added the initial dose of 40 mg of rusfertide administered twice a week to their regimen whether or not they obtained concurrent therapy. Once the subject’s hematocrit reached below 45%, the rusferitde dosage was given weekly and was adjusted to maintain hematocrit below 45%.

In an interview with Targeted OncologyTM, Yelena Ginzburg, MD, an associate professor of Medicine, Hematology and Medical Oncology at Mount Sinai, discussed the research and use of rusfertide in patients with PV, which she presented during ASH.

Targeted Oncology: Can you start off by kind of explaining the prognosis of patients with polycythemia vera and hematocrit above 45%?

Polycythemia vera is a chronic myeloproliferative disease, one of several. It is associated often given its chronicity with a long period of survival, including sometimes up to 20 years post diagnosis. There are groups of patients both better categorized into low risk versus high risk. The low-risk patients are younger and do not have a history of thromboembolic events. The higher risk population is older and/or has a history of a thromboembolic event. Patients are often treated with therapeutic phlebotomy, that's the mainstay of treatment, especially in the low-risk population. In the high-risk population, patients are often treated with cytoreductive agents of which hydroxyurea and interferon are both first line and ruxolitinib [Jakafi] is considered second line. So, despite cytoreductive therapy, some patients still require high levels of therapeutic phlebotomy and there is some risk of thrombosis that's higher in patients who require a higher rate of therapeutic phlebotomy.

What was the rationale for using rusfertide as treatment of these patients?

So the several talks at the ASH meeting this past weekend included several abstracts both regarding the ongoing phase two trial of rusfertide in phlebotomy requiring polycythemia vera patients as well as a newer trial that looked not at well controlled PB patients, meaning Patients with hematocrit going into the trial of below 45%, which is our target, but also patients who have not had perhaps access or have not availed themselves of the therapeutic phlebotomy option in a subgroup of patients. Those patients had a hematocrit well above 45% being enrolled into the trial precisely. We enrolled patients that had a hematocrit above 48% on at least two occasions at the time of inclusion in the trial. So, the circumstance in which rusfertide has been evaluated is in both low risk as well as high risk patients who continue to require at least three phlebotomy in the six months prior to study enrollment.

What else is important to note about this study design and the methods used?

The second trial and the trial where rusfertide was evaluated in a patient population that had not yet reached a hematocrit of 45, meaning had not received sufficient therapy to be well controlled with a high amount of hematocrit below 45%.The study evaluated the acute use of rusfertide at a dose of 40 milligrams subcutaneously administered twice a week. And after 2 consecutive values below 45%, it was the physician's discretion to decrease the dose either to weekly or to every other week. The data does suggest that there was a rapid and consistent decrease in hematocrit in patients who were enrolled who had hematocrit above 48%.

What were the results of the study that you presented during ASH?

Again, the study shows that the hematocrit was rapidly and persistently controlled with the initial dose of 40 milligrams twice weekly, that was effectively converted to a maintenance dose in the vast majority of patients within 4 to 12 weeks.

What did you observe in terms of safety in this study?

Ginzburg: The adverse events adjudicated to be related to the agent were all grade one and two. There was one patient with asymptomatic thrombocytosis that did not require any intervention. And the majority of the adverse events were injection site reactions, none of which led to the patients experiencing that side effect to come off of the study and were all relatively transient.

What are the key points that you want other oncologists to take away from this?

I think the main point that we are hoping to see with the trial as it continues is both a prolonged continuous either phlebotomy-free or phlebotomy-reducing effect of using rusfertide in the chronic setting that can also ultimately allow us to evaluate a potential reduction in the thrombotic events in this patient population. So, if the patients who require high levels of phlebotomy have a higher risk of thrombosis in this PV population, then reducing the need for therapeutic phlebotomy may uncover a significant reduction in the risk of thrombotic events in this patient population. Although that requires a longer time for evaluating and it is not really an endpoint that is required, we are hopeful that the use of this agent will eventually increase that additional benefit for this patient population.

Are there any plans to continue or confirm this research in another study?

Not that I'm aware of at the moment but there is a phase 3 trial that's planned to begin in 2022 using rusfertide in phlebotomy requiring PV patients.

What abstract coming out of ASH do you think has the biggest potential to change the standard of care for PV or myeloproliferative neoplasms?

There are a lot of agents that are coming through the pipeline. I think ultimately there's certainly room for rusfertide as a novel agent that may be paradigm shifting for low-risk phlebotomy requiring patients who often suffer from symptomatic iron deficiency that this agent is able to reverse, as well as the symptoms of both PV and systemic iron deficiency that appear to be better on this agent based on statistically significant decreases in symptom scores. I think rusfertide certainly is novel and poised for changing the paradigm, the toolkit, for what options exist for PV patients.

What excites you about the future of PV research and clinical treatment?

I'm very pleased that there are efforts being put into evaluating novel approaches to treating chronic malignancies by focusing on some of the mechanisms that we've learned within the context of iron metabolism over the last 20 years.


Ginzburg Y, Kirubamoorthy K. Salleh S, et al. Rusfertide (PTG-300) induction therapy rapidly achieves hematocrit control in polycythemia vera patients without the need for therapeutic phlebotomy. Blood. 2021;138(suppl 1):390. doi: 10.1182/blood-2021-149205

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