Divesiran Shows Clinical Responses in Phase 2 Polycythemia Vera Trial

Divesiran, a first-in-class small interfering RNA (siRNA) therapy, met the primary end point of the phase 2 SANRECO trial (NCT05499013) in patients with polycythemia vera (PV), according to a news release from Silence Therapeutics.¹

What did the phase 2 SANRECO trial show?

The primary end point was the proportion of patients achieving a response, defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18 to 36. In the 36-week, randomized, double-blind, placebo-controlled portion of the trial, a significantly higher proportion of patients treated with divesiran achieved a response vs those given placebo (88% vs 19%; P <.0001), corresponding to a placebo-adjusted response rate of 69%. Both dose groups showed substantial efficacy, with response rates of 93.8% at dosing every 6 weeks and 81.3% at dosing every 12 weeks.

The key secondary end point of phlebotomy rate during weeks 0 to 36 was also met, with the mean number of phlebotomies per patient significantly reduced in the divesiran groups vs placebo (0.2 vs 2.1; P <.0001). Divesiran was also associated with improvements in hematocrit control, iron markers including ferritin, and patient-reported outcomes measured by the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.

What was the safety profile of divesiran?

Divesiran was observed to be well tolerated, as safety was consistent with previous trials. There were no new safety findings. Injection site reactions were infrequent and self-limiting. Two investigator-reported cases of grade 1 anemia were observed.

The company plans to initiate a phase 3 trial evaluating divesiran vs placebo 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 patients [dependent on phlebotomy] 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 the press release.¹ “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 the SANRECO trial design?

The phase 2 portion of SANRECO is an ongoing, 3-part, global, randomized, placebo-controlled, double-blind study evaluating divesiran in 48 patients with phlebotomy-dependent PV. The trial assessed divesiran at 6 mg/kg administered subcutaneously every 6 weeks or every 12 weeks in patients with uncontrolled hematocrit who remained phlebotomy dependent despite standard-of-care treatment, which could include hydroxyurea, interferon, and/or ruxolitinib (Jakafi).² All patients have completed the placebo-controlled portion of the trial and are now in the 3-year double-blind and open-label extension periods. The developers plan to present full results at an upcoming medical congress.

What is divesiran and how does it work?

Divesiran is an siRNA candidate developed from an mRNAi GOLD platform that silences TMPRSS6, which is expressed almost exclusively in the liver and acts as a negative regulator of hepcidin, the body’s master regulator of iron metabolism. By silencing TMPRSS6, divesiran may increase hepcidin production, restricting iron availability to the bone marrow and thereby reducing the excessive production of red blood cells.

According to the press release, divesiran has previously received FDA fast track and orphan drug designations for PV. The developers noted that there are currently no approved therapies that specifically target red blood cells and hematocrit in PV, for which the standard of care includes repeated phlebotomies and cytoreductive agents.

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 11, 2026. https://tinyurl.com/yz5ypmz2
2. Study to assess SLN124 in patients with polycythemia vera (SLN). ClinicalTrials.gov. Updated December 19, 2025. Accessed August 11, 2026. https://tinyurl.com/d23w63s7