Silence Therapeutics announced positive topline results from the phase 2 SANRECO trial of divesiran, a first-in-class short interfering RNA (siRNA) therapy, in 48 phlebotomy-dependent patients with polycythemia vera (PV), the company announced August 10, 2026.¹ The trial met its primary endpoint, with 88% of divesiran-treated patients achieving a clinical response compared with 19% of patients on placebo, a placebo-adjusted response rate of 69% (p<0.0001).¹
Key facts
- Drug: Divesiran (SLN124; Silence Therapeutics)
- Class: First-in-class siRNA (silences TMPRSS6)
- Indication studied: Phlebotomy-dependent polycythemia vera
- Trial: SANRECO; phase 2, 48 patients
- Primary endpoint met: 88% response (divesiran) vs 19% (placebo); p<0.0001
- Dose-specific results: 93.8% (Q6W) vs 81.3% (Q12W) response rates
- Key secondary endpoint: 0.2 vs 2.1 phlebotomies per patient; p<0.0001
- Safety: Well tolerated; 2 grade 1 anemia cases; no new signals
- Regulatory status: FDA fast track and orphan drug designations (PV)
- Next milestone: Phase 3 trial (Q12W vs placebo) planned for 1H 2027
"Across the SANRECO phase 1/2 program, divesiran has been well tolerated and has consistently delivered durable hematocrit control in phlebotomy-dependent patients with PV, regardless of risk level or disease severity," said Marina Kremyanskaya, MD, PhD, associate professor of medicine, hematology and medical oncology, at the Icahn School of Medicine at Mount Sinai, in a company press release.¹
Why is a new treatment needed for polycythemia vera?
PV is a rare blood cancer marked by excessive red blood cell production, often resulting in elevated hematocrit; levels above 45% are associated with a 4-times higher rate of death from cardiovascular and thrombotic events.¹ Current standard of care relies on repeated phlebotomies and cytoreductive agents to reduce red blood cell production, and no approved therapies specifically target red blood cells or hematocrit directly.¹
What did the phase 2 SANRECO trial show?
The 36-week, randomized, double-blind, placebo-controlled portion of the trial evaluated divesiran, dosed subcutaneously at 6 mg/kg, administered every 6 weeks (Q6W) or every 12 weeks (Q12W). Response was defined as the absence of phlebotomy with hematocrit maintained below 45% during weeks 18-36; response rates were 93.8% for Q6W and 81.3% for Q12W.¹ The key secondary endpoint, phlebotomy rate during weeks 0-36, was also met, with a mean of 0.2 phlebotomies per patient in the divesiran groups compared with 2.1 for placebo (P<0.0001). Divesiran groups also showed improvements in ferritin and other iron markers and in patient-reported symptoms measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score.¹
How does divesiran work, and what is known about its safety?
Divesiran silences TMPRSS6, a negative regulator of hepcidin, the body's master regulator of iron metabolism. By increasing hepcidin production in the liver, it restricts iron availability to the bone marrow and reduces excessive red blood cell production.¹ In the phase 2 trial, divesiran was well tolerated with no new safety findings; injection site reactions were infrequent and self-limiting, and investigators reported 2 cases of grade 1 anemia.¹ These results are consistent with the phase 1 portion of SANRECO, in which divesiran was well tolerated without dose-limiting toxicities across 19 patients dosed at up to 9 mg/kg.²
