Topline Results From the SANRECO Trial Testing Divesiran in Polycythemia Vera

Marina Kremyanskaya, MD, PhD, Associate Professor at Icahn School of Medicine at Mount Sinai, discusses the phase 2 topline findings from the SANRECO clinical trial and the evolving polycythemia vera (PV) treatment landscape. PV is a condition characterized by an increased production of red blood cells. Affected people may also have excess white blood cells and platelets. The excess cell levels lead to thicker blood and increased risk for serious thrombotic events and stroke. PV occurs more frequently in men than it does in women. The condition has been associated with genetic changes in the *JAK2* and *TET2* genes. The SANRECO clinical trial is a phase 2, 36-week, randomized, double-blind, placebo-controlled trial evaluating divesiran (6 mg/kg) administered subcutaneously every six weeks (Q6W) or every twelve weeks (Q12W) in 48 phlebotomy-dependent patients with PV. Divesiran is a first-in-class siRNA designed to silence the *TMPRSS6* gene, thereby increasing hepcidin production and its release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells. The study met its primary endpoint, with 88% of patients achieving a response among divesiran-treated patients with PV, compared to 19% of those who received placebo. The primary endpoint was the proportion of patients achieving a response, defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18-36. Both 6 and 8 week dosing schedules showed substantial primary endpoint efficacy with response rates of 93.8% and 81.3% for Q6W and Q12W, respectively. The key secondary endpoint of phlebotomy rate during weeks 0-36 was also met with the mean number of phlebotomies per patient in the divesiran groups significantly reduced at 0.2, compared to placebo at 2.1. Divesiran groups also showed improvements in hematocrit control, iron markers including ferritin, and patient reported outcomes using the MPN-SAF Total Symptom Score. Divesiran was well tolerated and safety was in line with previous trials. No new safety findings were observed in the trial. Injection site reactions were infrequent and self-limiting. There were two investigator reported grade 1 anemia adverse event cases. For more information, click here. To learn more about PV and other rare hematologic disorders, visit https://checkrare.com/diseases/hematologic-disorders/ **Rare Discussions is produced by CheckRare**, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community. Explore additional physician interviews, podcasts, CME activities, and rare disease resources at **CheckRare.com**. Subscribe to the **CheckRare Podcast Network** for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community. Part of the **CheckRare Podcast Network**: Trusted conversations, news, education, and expert insights across the rare disease community.