Rona Therapeutics announced positive results from its Phase 1 clinical trial of RN0191, a novel siRNA therapy targeting PCSK9, at the American Heart Association's (AHA) Annual Scientific Sessions. The study demonstrated significant reductions in LDL-C and other lipid parameters with a favorable safety profile, suggesting potential as a bi-annual treatment for hypercholesterolemia.
The Phase 1 trial was a randomized, single-dose ascending, placebo-controlled study involving 32 healthy adults aged 18-60 with elevated LDL-C (ranging from 110-130 mg/dL). Participants received a single subcutaneous injection of RN0191 at doses ranging from 60mg to 600mg. The primary objectives were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN0191.
Significant and Durable Lipid Reduction
RN0191 exhibited dose-dependent reductions in PCSK9 and LDL-C levels. The mean maximum reduction of PCSK9 exceeded 85%, while LDL-C saw a mean maximum reduction greater than 55%. Notably, LDL-C reduction remained significant at 42% through Day 180, suggesting a potential for bi-annual dosing.
Beyond LDL-C, the study also observed significant reductions in ApoB, Lp(a), non-HDL-C, and total cholesterol. The effects on PCSK9, LDL-C, and other lipid parameters were sustained for up to six months following a single dose.
| | Placebo | 60mg | 200mg | 400mg | 600mg |
| :---------- | :------ | :---- | :---- | :---- | :---- |
| PCSK9 | | | | | |
| Mean Max Change (%) | -10% | -64% | -79% | -86% | -87% |
| Mean Change (%), Day 85 | -4% | -33% | -69% | -79% | -83% |
| Individual Max Change (%) | -50% | -81% | -87% | -91% | -95% |
| LDL-C | | | | | |
| Mean Max Change (%) | -6% | -23% | -48% | -56% | -51% |
| Mean Change (%), Day 85 | -6% | -20% | -36% | -47% | -45% |
| Individual Max Change (%) | -20% | -63% | -61% | -71% | -74% |
Safety and Tolerability
RN0191 demonstrated a favorable safety profile in the Phase 1 trial. No serious adverse events were reported, and only mild, transient adverse events were observed across all dose levels.
Implications for Atherosclerotic Cardiovascular Disease
"We are thrilled to report that RN0191 has demonstrated best-in-class PCSK9 siRNA potential," said Stella Shi, CEO of Rona Therapeutics. "These results highlight RN0191's potential as a transformative siRNA therapy for global patients with elevated LDL-C, a major risk factor for atherosclerotic cardiovascular disease either as single agent therapy or as combinatory backbone to improve cardiovascular outcome."
With millions globally affected by atherosclerotic cardiovascular disease and high LDL-C, new therapeutic options are needed. RN0191's ability to significantly and durably lower LDL-C with a potentially convenient bi-annual dosing regimen could represent a significant advancement in the field.
