The SANRECO phase II trial of divesiran, a first-in-class siRNA, in 48 phlebotomy-dependent patients with polycythemia vera, met its primary endpoint and secondary endpoints. The 36-week, randomized, double-blind, placebo-controlled portion of the trial administered divesiran subcutaneously (6 mg/kg) every six weeks or every twelve weeks.
Divesiran is sponsored by Silence Therapeutics.
Key findings from the study include:
- The primary endpoint was met, with a significantly higher proportion of clinical responders among divesiran-treated patients with PV compared to those who received placebo (88% for divesiran versus 19% for placebo; p<0.0001). The primary endpoint was the proportion of patients achieving a response, which was defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18-36.
- Importantly, both divesiran dose groups 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 compared to placebo (0.2 for divesiran versus 2.1 for placebo; p<0.0001).
- 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 observed to be 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 investigators who reported grade 1 anemia adverse event cases.
“Across the SANRECO phase I/II program, divesiran has been well tolerated and has consistently delivered durable hematocrit control in phlebotomy-dependent patients with PV, regardless of risk level or disease severity,” Marina Kremyanskaya, associate professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai, said in a statement. “These compelling results highlight divesiran’s potential to transform PV management with convenient, infrequent dosing that reliably controls hematocrit and addresses longstanding unmet needs for patients.”
“The SANRECO phase II trial delivered our best-case outcome, confirming the impressive results observed in phase I with dosing every six weeks and demonstrating equally robust and durable effects with quarterly dosing,” Curtis Rambaran, chief medical officer at Silence, said in a statement. “These results reinforce divesiran’s potential to become the first and best-in-class siRNA treatment for PV. We look forward to initiating phase III development and bringing divesiran to patients as quickly as possible.”
Silence plans to present full results from the phase II SANRECO trial at an upcoming medical congress.
