Silence Therapeutics plc (Nasdaq: SLN) reported positive topline results from the Phase II SANRECO trial of divesiran in polycythemia vera (PV) on August 10, 2026, with an 88% clinical response rate versus 19% for placebo, supporting advancement of the subcutaneous siRNA into Phase III development with dosing every twelve weeks.
Divesiran silences TMPRSS6, a hepatic gene that negatively regulates hepcidin, the master regulator of iron metabolism. By suppressing TMPRSS6, the drug raises hepcidin levels, restricting iron delivery to the bone marrow and thereby reducing the excessive red blood cell production that defines PV. The approach is mechanistically distinct from both Incyte's Jakafi (ruxolitinib), a JAK1/2 inhibitor approved for hydroxyurea-refractory PV, and PharmaEssentia's Besremi (ropeginterferon alfa-2b-njft), a pegylated interferon approved broadly for PV adults.
The 36-week, randomized, double-blind, placebo-controlled trial enrolled 48 phlebotomy-dependent patients who remained inadequately controlled on standard-of-care treatment, including hydroxyurea, interferon, and/or ruxolitinib. The primary endpoint — proportion of patients maintaining hematocrit below 45% without phlebotomy during weeks 18 to 36 — was met with statistical significance (p<0.0001), with a placebo-adjusted response rate of 69%. Both dosing regimens performed: the every-six-week arm achieved a 93.8% response rate and the every-twelve-week arm 81.3%. On the key secondary endpoint, mean phlebotomies per patient fell to 0.2 in divesiran-treated patients versus 2.1 in the placebo group (p<0.0001). The company reported no new safety findings; injection site reactions were infrequent and self-limiting, and only two Grade 1 anemia events were investigator-reported.
Phase I data presented at ASH 2024 and subsequently updated at the European Hematology Association congresses in 2025 and 2026 have demonstrated durable hematocrit control and reduced phlebotomy requirements with every-six-week dosing. The Phase II results extend those findings to every-twelve-week administration, which achieved an 81.3% response rate despite halving the dosing frequency. If maintained in Phase III, the regimen could differentiate divesiran on dosing frequency from ruxolitinib, which is taken orally twice daily, and ropeginterferon, which is administered subcutaneously every two to four weeks.