Andrew Kuykendall, MD, on Hepcidin Mimetic for Polycythemia Vera

Hi, my name is Andrew Kuykendall from Moffitt Cancer Center in Tampa, FL. And this year at ASCO, I'll be presenting the primary results from the phase three clinical trial called the VERIFY study, which is looking at the treatment of patients with polycythemia vera with rusfertide versus placebo in patients that are requiring phlebotomies for the treatment of their disease. This is an interesting study that was built upon the phase two REVIVE study which took patients with polycythemia vera who were requiring phlebotomies and put them on an agent called rusfertide, which is a hepcidin mimetic. Hepcidin, if everyone remembers, is something that we often like to forget after medical school, but it's an agent that really is the master regulator of iron. And in patients that have low iron, they often tend to have low hepcidin levels and iron is freely kind of exported and given to the bone marrow. Polycythemia vera represents a unique state where patients have systemic iron deficiency, but they actually overproduce red blood cells. And this is interesting because that overproduction of red blood cells actually burdens patients and puts them at risk for cardiovascular events. We know that one critical component of controlling this disease is actually to maintain the hematocrit or the red blood cells proportion of red blood cells in the blood at a level below 45%. And this protects patients from cardiovascular events. We also know that that kind of systemic iron deficiency seems to be associated with a variety of symptoms for patients including brain fog, fatigue and overall decreased quality of life. Our hypothesis with this agent was to think about kind of mimicking hepcidin to mimic a high hepcidin state thereby withholding iron from the bone marrow, controlling hematocrit and allowing kind of more normal regulation of iron throughout the body to allow other iron-requiring tissues to get the iron they need. And hopefully this would improve symptoms. So in this phase three trial, patients who were requiring phlebotomy were randomized to rusfertide versus placebo and continued their ongoing standard of care therapy. The primary endpoint was looked at from weeks 20 to 32. And the primary endpoint was really looking at patients whether or not they were eligible for phlebotomy. What we found is that rusfertide significantly reduced the phlebotomy eligibility of patients and maintained control of their hematocrit during this period of time compared to placebo. Ultimately VERIFY met its primary endpoint and all key secondary endpoints that looked at other measures of controlling hematocrit in addition to patient-reported outcomes. The two primary patient-reported outcomes that we looked at were the PROMIS fatigue score as we know that fatigue is something that plagues our patients with polycythemia vera as well as the MFSAF which is a validated symptom assessment form used for patients with myeloproliferative neoplasms. For both of these key secondary endpoints, patients who were randomized to rusfertide showed improvement in these patient-reported outcomes compared to what we saw with placebo, suggesting an improvement in their overall quality of life. So far at this meeting, we're presenting the results from phase one from Part 1A of this study. However, this is an ongoing study with Part 1B where all patients will go on open-label rusfertide and then be followed over in Part 2 of the study for a long-term safety assessment. In conclusion, this is really an interesting agent that I think has the potential to be added to current standard and modify the current standard of care and be used as an alternative to phlebotomy, which is truly an archaic way to treat our patients with polycythemia vera. We aim to further follow these patients in further aspects of the study to maintain and verify the safety of this data and look forward to presenting at future conferences as well.