A Revolutionary RNA-Based Treatment Emerges

In an exciting breakthrough for polycythemia vera (PV) management, a novel RNA-based therapy, Divesiran, is drawing attention from researchers and clinicians alike. Dr. Marina Kremyanskaya, an associate professor at Mount Sinai Hospital, sheds light on this promising development during her interview.

Divesiran's Role in the SANRECO Trial

The ongoing phase 1/2 SANRECO trial is at the forefront of this advancement. Divesiran is a GalNAc-conjugated small interfering RNA (siRNA) designed specifically to silence genes that contribute to the pathology of PV. Early findings presented at the upcoming 2025 EHA Congress emphasize its safety and tolerability at doses up to 9 mg/kg, showing great promise in managing this challenging condition.

Elevating Hepcidin Levels for Better Outcomes

Divesiran operates by increasing hepcidin levels in the bloodstream, which in turn regulates iron availability in the bone marrow. This unique mechanism curbs the production of red blood cells, ultimately leading to lower hematocrit levels and fewer required phlebotomies for patients. Dr. Kremyanskaya highlights how this innovative agent could redefine treatment strategies, especially for those who have not responded well to traditional therapies.

How Does Divesiran Work?

By targeting the mRNA of TMPRSS6—a negative regulator of hepcidin—Divesiran effectively diminishes its expression. The result? An enhanced production of hepcidin, which restricts the iron supply for red blood cell formation. This indirect approach sets Divesiran apart from traditional hepcidin therapies.

The Current Study Framework

The SANRECO trial incorporates three patient cohorts, composed of individuals heavily reliant on phlebotomy to manage their PV symptoms. Entry criteria include patients needing at least three phlebotomies in the past six months. While safety remains the primary focus, researchers are also keen on evaluating efficacy.

Positive Safety and Efficacy Signals

Participants have reported favorable outcomes, with injection-site reactions being the most common mild side effect. Impressively, no severe adverse events have led to discontinuation of treatment. More significantly, preliminary data indicates a notable reduction in the number of phlebotomies needed, particularly among patients who entered the trial with controlled hematocrit levels.

What’s Next for Divesiran?

As excitement grows, phase 2 enrollment is actively underway at multiple sites worldwide. This next phase aims to rigorously assess the drug against a placebo and varying dosing schedules, with results eagerly anticipated by year-end.

A Brighter Future for Polycythemia Vera Patients

The implications of Divesiran are extensive. If successful in ongoing trials, it could vastly improve the quality of life for patients suffering from frequent phlebotomies, potentially alleviating iron deficiency and reducing thrombotic risks. The future looks promising as this innovative RNA-based approach paves the way for new treatment avenues in polycythemia vera.