Silence Therapeutics' Divesiran Hits Phase II Goal, Sets Up Phase III PV Trial

Silence Therapeutics’ Divesiran Hits Phase II Goal, Sets Up Phase III PV Trial

Divesiran met the Phase II SANRECO primary endpoint in phlebotomy-dependent polycythemia vera, with 88% of treated patients maintaining hematocrit below 45% without phlebotomy versus 18% on placebo. The treatment substantially reduced phlebotomy needs: more than 90% of divesiran patients required none through week 36, compared with 12.5% of placebo patients. It also improved hematocrit control, iron-metabolism markers and quality-of-life measures. Silence reported no new safety concerns and plans to seek FDA guidance by year-end before launching a Phase III trial in the first half of 2027, likely testing a quarterly dosing schedule.

Silence Therapeutics NASDAQ: SLN reported top-line results from its Phase II SANRECO trial of divesiran in patients with phlebotomy-dependent polycythemia vera, or PV, with the study meeting its primary endpoint and supporting the company’s plan to advance a quarterly dosing regimen into Phase III. PV is a rare myeloproliferative neoplasm in which elevated hematocrit levels can increase health risks. According to Chief R&D Officer Steven Romano, treatment is intended to keep hematocrit below 45%, often through therapeutic phlebotomy. SANRECO enrolled 48 patients who met World Health Organization criteria for PV and were considered phlebotomy-dependent, defined as having received at least three phlebotomies in the prior six months or five in the prior year.

Primary Endpoint Results The randomized, double-blind Phase II portion of SANRECO evaluated divesiran at 6 mg/kg administered every six weeks or every 12 weeks, compared with placebo. The primary endpoint was the proportion of patients maintaining hematocrit below 45% without requiring phlebotomy during weeks 18 through 36. Romano said 88% of patients receiving divesiran across the combined active-treatment arms met the response criteria, compared with 18% of patients receiving placebo. The company reported a placebo-adjusted difference of nearly 70 percentage points and a p-value of less than 0.0001. Both dosing schedules showed high response rates. The every-12-week arm had a response rate above 80%, while the every-six-week arm exceeded 90%, according to Romano. Although the study was powered to compare the combined active arms with placebo rather than each individual dosing arm with placebo, he said both schedules appeared to have “relatively similar” effects in the smaller individual groups. A sensitivity analysis involving 40 patients who met the same phlebotomy-dependence criteria used in the company’s earlier Phase I study produced a divesiran response rate of nearly 90%, Romano said.

Phlebotomy and Secondary Measures The mean number of phlebotomies from week zero through week 36 was 0.2 among patients in the combined divesiran arms, compared with 2.1 among placebo patients. More than 90% of divesiran-treated patients did not require any phlebotomies during that period, versus 12.5% of placebo-treated patients. Silence also said divesiran-treated groups showed improvements in secondary measures including hematocrit control, markers of iron metabolism such as ferritin, and patient-reported quality-of-life outcomes. The company plans to present more detailed data at future scientific meetings, including the American Society of Hematology meeting in New Orleans in December. On symptom data, Romano said results from quality-of-life instruments, including measures focused on fatigue, were moving “in the right direction.” He said the company expects to use the Phase II findings to inform assumptions for a potentially more robustly powered symptom assessment in Phase III.

Safety Profile and Phase III Pla...