Silence Therapeutics’ divesiran met the Phase 2 SANRECO endpoint in polycythemia vera, with 88% clinical response versus 19% with placebo.
Written by: Anshu Gupta, PharmD
Reviewed by: Pharmacally Editorial Team
Silence Therapeutics’ investigational siRNA therapy divesiran met the primary endpoint in the Phase 2 SANRECO trial in patients with polycythemia vera (PV), with 88% of patients receiving divesiran achieving a clinical response compared with 19% receiving placebo.
The 36-week randomized, double-blind, placebo-controlled portion of the trial evaluated subcutaneous divesiran at 6 mg/kg administered every six weeks (Q6W) or every 12 weeks (Q12W) in 48 phlebotomy-dependent patients with PV.
The company said the study met its primary and key secondary endpoints, supporting plans to advance divesiran into Phase 3 development.
Divesiran Improves Hematocrit Control
The primary endpoint assessed the proportion of patients achieving a clinical response during weeks 18–36. A response was defined as the absence of phlebotomy and maintenance of hematocrit below 45%.
Overall, 88% of patients treated with divesiran achieved a clinical response compared with 19% of placebo-treated patients (p<0.0001), corresponding to a placebo-adjusted response rate of 69%.
Both dosing regimens demonstrated substantial activity. The clinical response rate was 93.8% with Q6W dosing and 81.3% with Q12W dosing.
The key secondary endpoint, which assessed the mean number of phlebotomies during weeks 0–36, also favored divesiran. Patients receiving divesiran underwent a mean of 0.2 phlebotomies per patient compared with 2.1 for placebo (p<0.0001).
Divesiran-treated patients also showed improvements in hematocrit control, iron markers including ferritin, and patient-reported symptoms measured using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS).
Trial Evaluated Phlebotomy-Dependent Patients
The Phase 2 portion of SANRECO (NCT05499013) is an ongoing, three-part, global, randomized, placebo-controlled, double-blind study evaluating divesiran in 48 phlebotomy-dependent patients with PV.
Participants had uncontrolled hematocrit despite standard-of-care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. All patients have completed the placebo-controlled portion of the trial and entered three-year double-blind and open-label extension periods.
PV is a rare myeloproliferative neoplasm characterized by excessive red blood cell production and elevated hematocrit. Maintaining hematocrit below 45% is an important treatment goal because higher levels are associated with increased cardiovascular and thrombotic risk.
Current treatment includes repeated phlebotomy and, when appropriate, cytoreductive agents. According to Silence, there are currently no approved therapies that specifically target red blood cells and hematocrit.
Divesiran Targets the TMPRSS6-Hepcidin Pathway
Divesiran is a small interfering RNA (siRNA) therapy designed to silence TMPRSS6, a gene expressed almost exclusively in the liver.
TMPRSS6 is a negative regulator of hepcidin, a key regulator of iron metabolism. By silencing TMPRSS6, divesiran is designed to increase hepcidin production and release by liver hepatocytes, restricting iron availability to the bone marrow and reducing the excessive production of red blood cells.
Divesiran is being developed using Silence Therapeutics’ proprietary mRNAi GOLD™ platform. The investigational therapy has received FDA Fast Track and Orphan Drug designations for PV.
Safety Findings Remain Consistent
Divesiran was reported to be well tolerated, with safety findings consistent with previous trials and no new safety findings observed during SANRECO.
Injection-site reactions were infrequent and self-limiting. Two investigator-reported grade 1 anemia adverse-event cases were also reported.
The company plans to present the full SANRECO results at an upcoming medical congress. The complete dataset will provide additional information on the efficacy and safety profile of divesiran.
Phase 3 Trial Planned for 2027
Silence Therapeutics plans to advance divesiran into Phase 3 development in PV. The company anticipates initiating a Phase 3 trial evaluating Q12W divesiran against placebo in the first half of 2027.
The longer-term SANRECO extension periods will continue to provide data on the durability of hematocrit control and the safety of repeated treatment.
Marina Kremyanskaya, MD, PhD, Associate Professor of Medicine in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, said the SANRECO findings were consistent with durable hematocrit control with infrequent dosing across patients with different risk levels and disease severity.
Silence Therapeutics Chief Medical Officer Curtis Rambaran, MD, said the Phase 2 results confirmed the findings observed in Phase 1 and demonstrated robust effects with both six-week and quarterly dosing.
The topline results support continued development of divesiran, but they do not establish comparative efficacy against existing standard-of-care therapies or confirm long-term clinical benefit. Further assessment will depend on the complete Phase 2 dataset and results from the planned Phase 3 program.
References
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.