Dr Kremyanskaya on the Ongoing Development of Divesiran for Polycythemia Vera

“We’re hoping that we will have [this class of] drugs available to patients who are with polycythemia vera, who [require] a lot of phlebotomies.”

Marina Kremyanskaya, MD, PhD, an associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai; as well as the medical director for the inpatient oncology unit at The Mount Sinai Hospital, discussed the development of divesiran (SLN124), an investigational therapy for patients with polycythemia vera (PV).

Findings from the phase 1/2 SANRECO trial (NCT05499013), which is currently enrolling internationally, are expected to further define the clinical role of this agent in reducing phlebotomy burden and improving hematocrit control in this population.

Preliminary results from the phase 1 portion of SANRECO demonstrated that divesiran administered every 6 weeks was associated with activity in limiting the need for phlebotomy and maintaining hematocrit levels within the target range in patients with PV. These data provided the basis for the ongoing randomized phase 2 portion of the study. In this phase, patients are being assigned to 1 of 3 treatment groups: divesiran every 6 weeks, divesiran every 12 weeks, or placebo, according to Kremyanskaya. She noted that the study is expected to complete enrollment by the end of 2025, with prospective, controlled results anticipated thereafter.

The rationale for investigating divesiran centers on its potential to address a key clinical challenge in PV: the reliance on frequent phlebotomy for hematocrit control. Patients who undergo repeat phlebotomies often develop iron deficiency, which contributes to fatigue and other disease-related symptoms, in addition to diminishing quality of life. By providing an alternative to intensive phlebotomy, divesiran may alleviate iron deficiency and improve hematologic control.

Kremyanskaya noted that effective management of hematocrit is central to reducing the risk of thrombotic events, the major cause of morbidity and mortality in patients with PV. Divesiran, if proven effective, could therefore serve as a means of lowering phlebotomy requirements and be used as a strategy to reduce thrombosis risk and its clinical consequences. Looking ahead, further results of SANRECO are expected to clarify the optimal dosing schedule for divesiran and its potential role as a new therapeutic option for patients with PV, she concluded.

Disclosures: Dr Kremyanskaya reported consulting roles with Silence Therapeutics, Protagonist, Incyte, Agios, Disc, and MorphoSys.