SANRECO phase I results: Divesiran, a first-in-class siRNA, in patients with PV

Patients with PV often require frequent phlebotomies and cytoreductive therapies to manage elevated hematocrit (HCT), which can cause symptoms such as fatigue, headaches, and pruritus. Hepcidin deficiency in PV leads to excessive iron utilization in the bone marrow and uncontrolled red blood cell production. 

Divesiran, a first-in-class GalNAc-conjugated siRNA targeting TMPRSS6 mRNA, is designed to increase hepcidin levels and rebalance iron distribution. The ongoing phase I/II SANRECO trial (NCT05499013) evaluates divesiran in adults with PV who required multiple recent phlebotomies. 

At the 2025 European Hematology Association (EHA) Congress, Marina Kremyanskaya presented findings from the completed phase I portion of SANRECO, with primary endpoints of assessed safety, tolerability, and preliminary efficacy in 21 participants across three dose-escalation cohorts (Cohort 1: 3 mg/kg, n = 6); Cohort 2: 6 mg/kg, n = 8), Cohort 3: 9 mg/kg, n = 7).¹

Key learnings

Divesiran reduced phlebotomies across all patients from 79 pre-treatment to 5 during treatment and 4 during follow-up; no patients with baseline HCT <45% (n=3) required phlebotomy post-treatment.

Mean HCT decreased from baseline across all dose cohorts, with reductions sustained through Day 232. Platelets increased from baseline by Day 29 across all cohorts (no dose dependency observed), and WBC counts were maintained.

Hepcidin levels increased from baseline across all cohorts, with greater increases observed in higher-dose groups; ferritin rose in previously iron-deficient patients (≤25 µg/L, n = 18), with one patient reaching 324 µg/L, indicating improved iron storage and redistribution.

Divesiran was well tolerated, with 83% of TEAEs being Grade 1 and no DLTs, SAEs, or TEAE-related discontinuations; the most frequent TEAE was injection site reaction (66.7%). These results support further investigation of divesiran for phlebotomy burden reduction in PV.