As reported on Fierce Biotech, Silence Therapeutics reported positive phase 2 findings for divesiran, an investigational small interfering RNA (siRNA) treatment for polycythemia vera (PV), a rare blood cancer marked by overproduction of red blood cells. The company plans to begin a phase 3 program in the first half of next year.
Divesiran is designed to suppress TMPRSS6 production in the liver. By altering iron availability to the bone marrow, the approach aims to reduce red blood cell production and help patients maintain appropriate hematocrit levels without repeated therapeutic blood removal procedures.
The placebo-controlled study enrolled 48 patients with PV who required phlebotomy to manage their disease. During weeks 18 through 36, 88% of participants treated with divesiran met the trial’s primary response measure, compared with 19% in the placebo group. Response required both avoiding phlebotomy and maintaining hematocrit below 45%.
Results were favorable across the two evaluated dosing schedules. Among patients receiving divesiran once every six weeks, 93.8% achieved a response; the rate was 81.3% among those treated every 12 weeks.
The treatment also reduced the need for phlebotomy. Patients receiving divesiran had a phlebotomy rate of 0.2, versus 2.1 for placebo recipients. Silence additionally reported better hematocrit management, improvements in iron-related biomarkers such as ferritin, and positive patient-reported outcomes. The company said no unexpected safety findings emerged during the study.
Divesiran’s development comes as rusfertide, a hepcidin-mimicking peptide developed by Protagonist Therapeutics and licensed to Takeda, approaches a potential U.S. launch. Takeda and Protagonist have submitted rusfertide for FDA review following phase 3 data showing a 76.9% response rate during weeks 20 to 32, compared with 32.9% for placebo. The partners anticipate a regulatory decision in the third quarter.
Takeda paid Protagonist $300 million upfront in 2024 for rights to rusfertide. If approved, the therapy could reach patients before Silence initiates its pivotal divesiran study.
Silence may seek to differentiate divesiran through a less frequent administration schedule. Rusfertide was administered by patients as a weekly injection in its phase 3 trial, while Silence intends to use every-12-week dosing for divesiran in phase 3.
As of the end of March, Silence reported $70.1 million in cash and short-term investments.
