Silence Therapeutics Reports Positive Phase 1 SANRECO Study Results for Divesiran in Polycythemia Vera

Silence Therapeutics plc ("Silence"), a pioneering biotechnology company, has announced encouraging outcomes from its ongoing SANRECO Phase 1 repeat dose study of divesiran (SLN124), a short interfering RNA (siRNA) targeting TMPRSS6, in patients suffering from polycythemia vera (PV). This announcement marks a significant step forward for the company, which aims to transform lives by developing precision-engineered medicines that silence disease.

Craig Tooman, President and CEO of Silence, expressed enthusiasm over the new data, stating that the results underscore Silence's potential as a platform company. Divesiran is on track to become the first siRNA therapy for PV, with plans to initiate Phase 2 by year-end.

The 34-week, open-label Phase 1 study involves administering divesiran (at doses of 3 mg/kg, 6 mg/kg, and 9 mg/kg) subcutaneously every six weeks for a total of four doses. This is followed by a 16-week observation period. The study includes up to 24 PV patients who have required multiple phlebotomies within the last year. Participants can continue stable doses of cytoreductive agents. Both well-controlled patients (with hematocrit levels at or below 45%) and those with higher baseline hematocrit levels were enrolled.

As of March 29, 2024, data analysis from 16 patients over 4 to 34 weeks of involvement showed promising results. Eight patients had well-controlled hematocrit levels at baseline, and the remaining eight had levels above 45%. No significant safety concerns were observed.

Among the eight well-controlled patients, none required phlebotomy during the treatment period, maintaining adequate hematocrit control as per guidelines. In the group with higher hematocrit levels, only two out of eight patients needed a single phlebotomy each. These two patients had baseline hematocrit levels of 56% and 53%. The other six patients did not require phlebotomy. Notably, none of the 13 patients with hematocrit levels of 50% or below needed phlebotomy during the study.

All dose groups showed a sustained reduction in hematocrit levels during the treatment period and positive effects on iron metabolism indices. Hepcidin levels increased and remained within physiological ranges, indicating successful target engagement.

Professor Tomas Ganz of UCLA highlighted that divesiran treatment in PV patients leads to sustained hepcidin increases, a crucial target engagement. The treatment showed beneficial effects on hematological parameters and a significant reduction in the need for phlebotomies, suggesting that divesiran could yield clinically meaningful outcomes.

Steven Romano, Head of Research and Development at Silence, emphasized the significance of these early findings. He noted that divesiran appears to positively impact key hematological parameters in PV, a rare myeloproliferative neoplasm. The safety profile and potential for infrequent administration were particularly encouraging.

To date, Silence has enrolled 21 patients in the SANRECO study and expects to close enrollment by the end of the month. Full results are anticipated to be presented at a scientific meeting later this year. Divesiran has received FDA Fast Track designation and FDA Orphan Drug Designation for PV.

Polycythemia vera is a rare blood cancer characterized by excessive red blood cell production, leading to elevated hematocrit levels and increased risk of cardiovascular and thrombotic events. Current treatment aims to maintain hematocrit below 45% to reduce these risks. However, there are no approved therapies specifically targeting red blood cells and hematocrit. Silence’s divesiran, developed from its proprietary mRNAi GOLD™ platform, aims to address this gap by silencing TMPRSS6, thereby increasing hepcidin production and reducing excessive red blood cell production.

Silence Therapeutics is dedicated to developing a new generation of medicines through RNA interference (RNAi) to inhibit disease-associated gene expression. Its proprietary mRNAi GOLD™ platform allows for the creation of siRNAs that target and silence disease-associated genes in the liver. In addition to divesiran, Silence’s product pipeline includes zerlasiran, aimed at reducing cardiovascular risk in individuals with high lipoprotein(a) levels. The company also collaborates with AstraZeneca and Hansoh Pharma on ongoing research and development projects.