Dr Kremyanskaya on the Efficacy of Divesiran in Polycythemia Vera

"The exciting result here is that these patients really don't seem to be really needing phlebotomy once they start on the study drug."

Marina Kremyanskaya, MD, PhD, associate professor of medicine in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, reported safety and early efficacy findings with divesiran (SLN124), an investigational therapy for patients with polycythemia vera (PV), based on results from the ongoing phase 1/2 SANRECO trial (NCT05499013).

Divesiran is a small interfering RNA (siRNA) designed to selectively reduce expression of the iron regulator TMPRSS6, potentially improving iron restriction and reducing erythrocytosis in PV. In SANRECO, divesiran was administered subcutaneously every six weeks for four doses, followed by a 16-week observation period. Kremyanskaya emphasized the convenience of this infrequent dosing schedule, which could represent a meaningful improvement for patients compared with more burdensome current therapies.

Treatment with divesiran was generally well tolerated. The most frequently observed adverse effect was injection-site reaction, which was mild, self-limited, and resolved without intervention in all patients. Importantly, there were no adverse events leading to treatment discontinuation or any serious events attributed to the study drug.

Early signs of efficacy were promising. Patients receiving divesiran required markedly fewer phlebotomies during the treatment period compared with both their baseline requirements and the observation period. Of particular note, patients who began the study with adequately controlled hematocrit levels (less than 45%) did not require any additional phlebotomies while on divesiran. This suggests that divesiran may be effective in maintaining hematocrit control and reducing phlebotomy burden—a primary goal in PV management.

Kremyanskaya highlighted that these preliminary data support further investigation of divesiran as a potential disease-modifying therapy in PV, offering a novel mechanism of action alongside an attractive dosing schedule and favorable tolerability profile.