Silence Therapeutics (SLN) Study result summary

Study overview and objectives

• The Phase II SANRECO trial was a global, randomized, double-blind, placebo-controlled study evaluating divesiran, a first-in-class siRNA therapy, in 48 phlebotomy-dependent polycythemia vera (PV) patients across nine countries and four continents.

• Patients were randomized 1:1:1 to receive divesiran 6 mg/kg every 6 or 12 weeks or placebo, with eligibility requiring PV diagnosis and frequent phlebotomies.

• The primary endpoint was the proportion of patients maintaining hematocrit <45% without phlebotomy during weeks 18–36.

• Secondary outcomes included safety, tolerability, pharmacokinetics, quality-of-life measures, phlebotomy rate, and iron markers.

• All patients completed the placebo-controlled portion and entered a 3-year extension period.

Key efficacy and safety results

• 88% of divesiran-treated patients achieved the primary endpoint versus 18–19% for placebo, with a placebo-adjusted response rate of 69% (p<0.0001).

• Both Q6-week and Q12-week dosing arms showed robust response rates (81.3–93.8%).

• Sensitivity analysis in stricter phlebotomy-dependent patients showed 89–90% response for divesiran versus 8% for placebo.

• Mean number of phlebotomies over 36 weeks was 0.2 for divesiran versus 2.1 for placebo; over 90% of treated patients required no phlebotomies.

• Divesiran improved hematocrit control, iron metabolism markers (including ferritin), and patient-reported outcomes (MPN-SAF TSS).

Safety and tolerability

• Divesiran was well tolerated with no major safety concerns or new safety issues; safety profile consistent with previous trials.

• Injection site reactions were infrequent, self-limiting, and grade 1.

• Two cases of grade 1 anemia occurred, both asymptomatic.

• Modest, expected platelet elevation (reactive thrombocytosis) observed, not considered a concern.

• No changes in white blood cell counts.