EHA 2025 | Early findings from the Phase I/II SANRECO study: divesiran in polycythemia vera

So the SANRECO trial is a phase 1-2 trial that is testing this new agent, divesiran, in patients with polycythemia vera that are heavily dependent on phlebotomies. So the results presented at EHA were the results for the phase 1 part of the study. So the eligibility criteria for the study is that patients had to have a diagnosis of polycythemia vera, and then they had to have at least three phlebotomies in the six months prior to enrollment, or five in the year prior. So the eligibility criteria are fairly simple. And then the design of the trial is that there were three cohorts of patients, those in three different levels of the drug. So three milligrams, six milligrams, and nine milligrams per kilogram. And the drug is administered as a subcutaneous injection that’s given every six weeks. So on trial, patients got four doses every six weeks, and then there was a 16-week observation period. So just a little bit about the mechanism of action of the drug. So this is the first time that this approach is being used, and the approach is used in small interfering RNA to block a negative regulator of hepcidin production called TMPRSS6. And so what this means is that there is an increased endogenous production of hepcidin. So this is different from a similar drug that’s been cited in this field, rusfertide, which is actually a hepcidin mimetic, where the hepcidin is basically given, resulting in increased hepcidin levels in the blood. In this case, the body is basically producing more hepcidin. And what that means is that in the setting of increased hepcidin, there’s a restriction of how much iron is available in the blood. And therefore, how much iron is available in the bone marrow for red blood cell production resulting in a decrease in erythropoiesis. And therefore, a decrease in red blood cell counts in hematocrit and eliminates the need for phlebotomy. So that’s kind of the background for the study. So what the study showed is that once patients were treated at all those levels, the number of phlebotomies significantly decreased. In fact, for those patients that had controlled hematocrit at baseline, so they started at a hematocrit of less than 45 when they entered the study, they never needed another phlebotomy when they were on study. So these are promising results. Looking at the levels of hepcidin as would be expected with this drug, the level of hepcidin went up in all those cohorts, more so in the higher levels, and looking at some of the iron parameters, patients on average, the level of ferritin was very low, which is what is usually seen in PV patients that require a lot of phlebotomies, and as they started on treatment, ferritin went up to normal levels, kind of suggesting that overall, there’s a redistribution of iron, and so while iron is overall restricted for erythropoiesis, it is presumably available for other cellular processes, which is why we are hoping that similar to the other drugs in this field, we will see an improvement in symptoms. This data is being collected and was not yet available. The drug is well tolerated, the most common side effect is the injection site reaction, which was self-limited, and phase two of this phase 1-2 study is currently enrolling patients and hoping to finish enrollment relatively soon, maybe by about the end of this year.

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