EHA 2023 | LBA: results of REVIVE – rusfertide in patients with polycythemia vera

So we will be presenting an update of the REVIVE study. Some of the results have been presented previously, but at the EHA congress, we’ll be presenting the update from the randomized portion of the study. So, REVIVE study is a Phase II study of hepcidin-mimetic rusfertide in patients with polycythemia vera that are heavily phlebotomy dependent. So the inclusion criteria for the study are fairly simple, patients have to have a diagnosis of polycythemia vera as per WHO criteria and then they need to have required three or more phlebotomies in the 28 weeks prior to enrollment.

And the study consists of three different parts. So the first part is basically the dose finding study – every patient starts on low dose of rusfertide, at 20 weekly, which is given as a subcutaneous injection weekly and then the dose is titrated every month to achieve a therapeutic dose for the patient to maintain the hematocrit at less than 45%. At week 29 patients start their part two of the study, which is called randomized withdrawal. So patients are randomized to either continue on their last therapeutic dose of rusfertide or they receive a placebo. And so patients continue on part two, either for the full duration of part two or until they require a phlebotomy. Once they require phlebotomy, they can start stop the randomized withdrawal part and they can enter the extension phase of the study which is open-label, and everybody receives the therapeutic dose of rusfertide.

So what will be presented at EHA is these results from the randomized withdrawal part of the study, which was the primary endpoint of the study, and the primary endpoint is defined as percentage of responders and patients who are getting rusfertide versus patients who are getting a placebo. So, the patient population, it includes patients who are low risk and patients that are high risk for polycythemia vera. So patients are either treated with therapeutic phlebotomy alone at baseline or they’re treated with therapeutic phlebotomy and cytoreductive therapy – so the study includes all comers. And what will be presented here is that all patients respond to treatment with rusfertide. It was first seen in part one of the study where it easily see that the number of phlebotomy events is basically eliminated once patients start on study and especially once they reach their own therapeutic dose. And then once the patients entered the randomized withdrawal part of the study, when we look at the responders, the difference between responders is about 69% in the rusfertide arm and 18% in the placebo arm. So, there is a statistically significant difference between the two arms. And in fact, some of the patients that were counted as non-responders in the study were moved over to the Part three of the study because of the patient investigator decision. But in fact they did not actually meet the eligibility criteria for the phlebotomy, so the actual response rate is even higher, as much as 90%. And so these results are very exciting because it shows in a randomized manner that rusfertide is much more effective in controlling hematocrit as opposed to the standard therapy that patients were getting prior to starting treatment.

Since the way that rusfertide works is a hepcidin mimetic, so hepcidin is a major regulator of iron metabolism, we also wanted to look at what happens with the different iron parameters. So the main component of iron studies is ferritin, which shows systemic iron stores, and for all patients that enter the study, the ferritin levels are very low when they begin because these patients have a phlebotomy dependence, so they tend to be very iron deficient. And once they start on study, once they’re treated with rusfertide, the levels of ferritin normalize, and they remain in the normal levels.

And so we also looked at the effects of rusfertide on symptoms. And the symptoms, specifically for those patients that are that have more moderate to severe symptoms at baseline, rusfertide improved certain types of symptoms such as pruritis and fatigue and difficulties concentration – and this data is from part one of the study. So in general, rusfertide is well tolerated. The major treatment emergent adverse events were injection site reactions, they were grade one and two, and patients were able to tolerate the injection site reactions as they tend to improve with ongoing treatment.

So the drug is well tolerated and the drug seems to be effective in this randomized cohort of patients. Currently, Phase III study of rusfertide is ongoing, where all patients are randomized to receive placebo or rusfertide, and of course the results of that study will be very important to see.