Divesiran Meets Primary Response End Point in Phlebotomy-Dependent Polycythemia Vera

Treatment with divesiran (SLN124), a first-in-clase short interfering RNA therapy, led to a significantly higher proportion of clinical responders compared with placebo in patients with phlebotomy-dependent polycythemia vera, meeting the primary end point of the phase 2 portion of the SANRECO trial (NCT05499013).¹

Findings announced by Silence Therapeutics showed that 88% of patients treated with divesiran achieved a response vs 19% of those given placebo (placebo-adjusted response rate, 69%; P < .0001). Notably, divesiran generated a response rate of 93.8% at the 6-mg/kg dose administered subcutaneously every 6 weeks and 81.3% for the 6-mg/kg dose administered every 12 weeks. Response was defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18 to 36.

The trial also met its key secondary end point of phlebotomy rate during weeks 0 to 36, with the mean number of phlebotomies per patient significantly reduced in the divesiran groups at 0.2 compared with 2.1 for placebo (P < .0001). Patients in the divesiran groups also experienced improvements in hematocrit control, iron markers including ferritin, and patient-reported outcomes measured by the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS).

Divesiran was observed to be well tolerated, with safety in line with previous trials and no new safety findings, the company reported. Injection site reactions were infrequent and self-limiting, and there were 2 investigator-reported cases of grade 1 anemia.

Silence plans to present full results from the SANRECO trial at an upcoming medical congress. A phase 3 trial evaluating divesiran dosed every 12 weeks vs placebo in patients with polycythemia vera is anticipated to initiate in the first half of 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,” Marina Kremyanskaya, MD, PhD, associate professor of medicine, hematology and medical oncology, at the Icahn School of Medicine at Mount Sinai in New York, New York, stated in a news release. “These compelling results highlight divesiran’s potential to transform PV management with convenient, infrequent dosing that reliably controls hematocrit and addresses longstanding unmet needs for patients.”

What is divesiran?

Divesiran is a first-in-class, wholly owned siRNA candidate developed from Silence’s mRNAi GOLD platform that silences TMPRSS6, a negative regulator of hepcidin expressed almost exclusively in the liver. By silencing TMPRSS6, divesiran aims to increase hepcidin production, restricting iron availability to the bone marrow and reducing the excessive red blood cell production that characterizes PV. The agent holds FDA fast track and orphan drug designations for polycythemia vera.

How was SANRECO conducted?

The phase 2 portion of SANRECO was a 3-part, global, randomized, double-blind, placebo-controlled study that evaluated divesiran in 48 patients with phlebotomy-dependent polycythemia vera; the overall phase 1/2 study enrolled 69 patients.^1,2

Eligible patients needed to be 18 years of age or older with a confirmed diagnosis of polycythemia vera per the revised 2016 World Health Organization criteria, uncontrolled hematocrit, and phlebotomy dependence despite standard-of-care treatment that could include hydroxyurea, interferon, and/or ruxolitinib (Jakafi).²

During the 36-week, randomized, double-blind, placebo-controlled portion, patients received divesiran at 6 mg/kg subcutaneously once every 6 or 12 weeks, or placebo.

The primary end point was the proportion of patients achieving a response during weeks 18 to 36; secondary end points included phlebotomy rate, hematology parameters and biomarkers of iron metabolism, and quality-of-life measures.

“The SANRECO phase 2 trial delivered our best-case outcome, confirming the impressive results observed in phase 1 with dosing every 6 weeks and demonstrating equally robust and durable effects with quarterly dosing,” Curtis Rambaran, MD, chief medical officer at Silence, added in a news release.¹ “These results reinforce divesiran’s potential to become the first and best-in-class siRNA treatment for PV.”

References

1. Silence Therapeutics announces positive topline results from phase 2 SANRECO trial of divesiran in polycythemia vera, supporting its potential best-in-class profile. News release. Silence Therapeutics plc. August 10, 2026. Accessed August 10, 2026. https://www.businesswire.com/news/home/20260810915756/en/Silence-Therapeutics-Announces-Positive-Topline-Results-from-Phase-2-SANRECO-Trial-of-Divesiran-in-Polycythemia-Vera-Supporting-its-Potential-Best-in-Class-Profile
2. Study to assess SLN124 in patients with polycythemia vera. ClinicalTrials.gov. Updated December 19, 2025. Accessed August 10, 2026. https://clinicaltrials.gov/study/NCT05499013