Phase 2 Study for Short Interfering RNA-Based PV Treatment Brings Welcome Results

SANRECO is a three-part, ongoing, global clinical trial to evaluate divesiran for treatment of polycythemia vera (PV). One component is a phase 2, randomized, placebo-controlled study of the agent in phlebotomy-dependent patients with disease that has withstood standard-of-care interventions. This study met its primary and key secondary end points and had favorable overall findings. The phase 2 study's results were announced in a press release by divesiran's developer, Silence Therapeutics plc, an international biopharmaceutical company headquartered in London, United Kingdom. Additional written remarks on the study were shared with Heme Today by its lead investigator, Marina Kremyanskaya, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York City. 'What makes divesiran especially exciting is that, although it targets the iron–hepcidin pathway like rusfertide, it does so through a first-in-class, potent siRNA [short interfering RNA] approach—introducing a novel mechanism of action for the treatment of PV,' Dr. Kremyanskaya wrote. The 36-week double-blind study's cohort comprised 48 patients with PV who had uncontrolled hematocrit, were phlebotomy dependent, and had received treatment with hydroxyurea, interferon, or ruxolitinib that was unsuccessful. Enrollees were randomized to receive subcutaneous divesiran 6 mg/kg every 6 weeks, every 12 weeks, or placebo. 'Responders were defined as patients who did not receive a phlebotomy and maintained hematocrit below 45% during weeks 18-36 of the study,' Dr. Kremyanskaya wrote. This response was observed in a greater proportion of the divesiran recipients than in the placebo group, at 88% versus 19%, respectively (P<0.0001), representing attainment of the study's primary end point. 'Interestingly, treatment with both Q6 weeks and Q12 weeks dosing was effective with response rates of 94% and 81% respectively,' Dr. Kremyanskaya wrote. 'Patient reported outcomes also showed improvements with divesiran treatment and the treatment was well tolerated overall.' Also notable in the study's efficacy outcomes was that over the course of the entire 36-week study, the average number of phlebotomies per patient markedly decreased in the divesiran group versus the placebo group, at 0.2 versus 2.1, respectively (P<0.0001), representing attainment of the study's key secondary end point. The study's specific safety results, in terms of adverse events, included two cases of grade 1 anemia. Injection site reactions tended to be uncommon and to resolve independently. Regarding next steps for SANRECO, Silence Therapeutics intends to present these phase 2 study data at a medical congress in the near future, and the larger trial aims to continue to a phase 3 study to compare divesiran dosing every 12 weeks with placebo. 'These are very exciting findings as this approach could potentially offer patients an effective, well tolerated treatment with very infrequent, once every 3 months dosing,' Dr. Kremyanskaya wrote. 'We would need to see these results confirmed in a larger phase 3 trial, which is planned to start in the first half of 2027.' References Silence Therapeutics. Accessed September 4, 2026. https://silence-therapeutics.com/investors/press-releases/press-releases-details/2026/Silence-Therapeutics-Announces-Positive-Topline-Results-from-Phase-2-SANRECO-Trial-of-Divesiran-in-Polycythemia-Vera-Supporting-its-Potential-Best-in-Class-Profile/default.aspx