The part 2 SANRECO examine has lately accomplished enrollment and can consider divesiran, a possible remedy for sufferers with polycythemia vera (PV), a blood most cancers characterised by extreme purple blood cell manufacturing. PV is classed as a myeloproliferative neoplasm (MPN), a kind of blood most cancers affecting the bone marrow.
This international, randomized, double-blind, placebo-controlled examine enrolled 48 sufferers with PV, with preliminary topline outcomes anticipated within the third quarter of 2026. To be taught extra concerning the trial, CURE spoke with Dr. Marina Kremyanskaya, the lead investigator of the SANRECO trial, to debate present standard-of-care choices for PV, the goals of the part 2 examine, the mechanism of divesiran, and extra.
Kremyanskaya is an affiliate professor of Drugs, Hematology and Medical Oncology, on the Icahn Faculty of Drugs at Mount Sinai in New York.
CURE: What’s the present normal of take care of sufferers newly identified with PV, and what challenges or limitations exist with these therapies?
Kremyanskaya: There are a number of completely different pathways that we may take. Sometimes, we have a look at a affected person and decide which danger class they match into. Considerably artificially, sufferers are divided into two teams: low danger and excessive danger, and that is actually primarily based on their danger of thrombosis, that means blood clots, sooner or later. It’s principally determined primarily based on their age. At 60 years previous, sufferers are thought of excessive danger, and if they’re youthful than that, they’re thought of low danger. A further danger issue is a earlier historical past of blood clots, so if sufferers have none of that, they’re thought of low danger.
The everyday therapy is therapeutic phlebotomy. Mainly, we bodily take away a number of the blood from the affected person in a course of related to what’s achieved when folks donate blood. The rationale for that is that blood counts are very excessive, which places sufferers at a better danger for thrombosis. It has been proven that by reducing the blood depend, particularly the purple blood cells, we will cut back their danger of thrombosis. Thrombosis, on this case, will be something, for instance, coronary heart assaults, strokes, or blood clots within the legs, lungs, or different components of the physique. These can have very severe penalties.
Sometimes, we even have sufferers take a low-dose aspirin as a light blood thinner to lower the danger of blood clots. If sufferers are greater danger, then along with phlebotomies, we’ve got a number of different therapy decisions. Considered one of them is hydroxyurea, which works to cut back all blood counts. Now we have been utilizing hydroxyurea for a lot of many years for various blood cancers, and it’s nonetheless generally utilized in PV. Different choices embrace interferon, which is available in a number of completely different formulations and is given as injections, and Jakafi (ruxolitinib), a more moderen drug that may be a JAK inhibitor. Jakafi is extra of a biologic remedy that particularly targets the activated pathway seen in these problems.
Whereas there are a number of completely different decisions, phlebotomy stays the cornerstone of therapy. Though it feels like there are lots of choices, the truth is that there are literally not that many.
What’s the main goal of the SANRECO scientific trial, and the way does it intention to handle unmet wants in PV administration?
What this scientific trial is doing is utilizing the pathway that’s vital for iron metabolism and management of iron within the physique to manage the variety of purple blood cells produced. As I discussed, the key situation for sufferers with PV is that the bone marrow is inappropriately making too many purple blood cells. Consequently, the blood turns into very thick, placing sufferers in danger for all of the issues we mentioned, in addition to many alternative signs (some not talked about), equivalent to fatigue, issue concentrating, itching, and lots of others. Each affected person experiences signs barely in another way.
This drug targets the pathway for the hormone hepcidin, which is a regulator of iron metabolism within the physique. Iron is essential for purple blood cell manufacturing. Sometimes, when iron is restricted, purple blood cell manufacturing decreases. That is why sufferers turn out to be iron poor and anemic after extreme bleeding. For instance, folks typically say, “I’m anemic. I have to take some iron.” This course of is regulated by hepcidin.
We all know that sufferers with PV even have decrease hepcidin ranges, which is anticipated on this situation. By rising hepcidin ranges, the quantity of iron obtainable within the bone marrow for purple blood cell manufacturing is minimized. Consequently, the bone marrow produces fewer purple blood cells. As a substitute of requiring phlebotomy to bodily take away blood, this method permits management of how a lot blood the bone marrow produces, thereby managing hematocrit and hemoglobin ranges. It represents a really completely different method to the therapy of PV.
Are you able to present an replace on the present standing of the SANRECO trial and what key milestones or outcomes we will anticipate within the close to future?
Section 2 is ongoing, and excitingly, simply completed enrollment, so all of the sufferers are enrolled. Now, we simply have to attend for the outcomes of the trial, so it is a very thrilling time for this drug.
Transcript has been edited for readability and conciseness.
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