Silence Therapeutics Reports Positive Phase 2 Results for Divesiran in Polycythemia Vera

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

"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

What's next for divesiran?

"The SANRECO phase 2 trial delivered our best-case outcome, confirming the impressive results observed in phase 1 with dosing every six weeks and demonstrating equally robust and durable effects with quarterly dosing," said Curtis Rambaran, MD, chief medical officer at Silence, in the release.¹ "We look forward to initiating phase 3 development and bringing divesiran to patients as quickly as possible."¹

The company plans to present full SANRECO phase 2 results at an upcoming medical congress and expects to initiate a phase 3 trial evaluating divesiran Q12W versus placebo in the first half of 2027.¹ Divesiran already holds FDA fast track and orphan drug designations for PV, and all phase 2 participants are now in 3-year double-blind and open-label extension periods.¹^,³

What are the limitations?

These are topline results from a small, 48-patient trial, and full data, including durability beyond 36 weeks, have not yet been presented or published. A phase 3 trial has not yet begun, and fast track designation does not necessarily guarantee eventual approval.

References

1. Silence Therapeutics. Silence Therapeutics announces positive topline results from phase 2 SANRECO trial of divesiran in polycythemia vera, supporting its potential best-in-class profile. Press release. Published August 10, 2026. Accessed August 11, 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
2. Kremyanskaya M, Hoffman R, Chew LP, et al. Initial results from a phase 1/2 study evaluating divesiran, a novel GalNAc-conjugated siRNA, in patients with polycythemia vera (SANRECO). Blood. 2024;144(suppl 1):656. doi:10.1182/blood-2024-205854
3. ClinicalTrials.gov. Study to assess SLN124 in patients with polycythemia vera (SLN). NCT05499013. Updated December 19, 2025. Accessed August 11, 2026. https://clinicaltrials.gov/study/NCT05499013