Rona Therapeutics' RN0361 siRNA Demonstrates 93% ApoC3 Reduction in Phase 1 Trial for Severe Hypertriglyceridemia
核心洞察
Rona Therapeutics (搜索) presented Phase 1 data for RN0361, a long-acting ApoC3-targeting siRNA that achieved up to 93% ApoC3 reduction and 69% triglyceride lowering lasting at least six months from a single dose.
The randomized, placebo-controlled study in volunteers with baseline triglycerides >80 mg/dl showed favorable tolerability with no serious adverse events and only mild injection-site reactions.
RN0361 demonstrated robust reductions in atherogenic lipoproteins including non-HDL cholesterol, VLDL cholesterol, and remnant cholesterol without affecting glucose metabolism.
Rona Therapeutics (搜索) presented compelling Phase 1 clinical data for RN0361, a long-acting siRNA targeting Apolipoprotein C3 (搜索) (ApoC3), at the American Heart Association 2025 Scientific Sessions in New Orleans. The first-in-human trial demonstrated that RN0361 achieved potent, durable reductions in ApoC3 and triglycerides lasting at least six months from a single dose, establishing a potential best-in-class profile for preventing pancreatitis in severe hypertriglyceridemia (搜索) and reducing cardiovascular risk.
Phase 1 Trial Results
The randomized, placebo-controlled Single Ascending Dose (SAD) study enrolled volunteers with baseline triglycerides >80 mg/dl and demonstrated favorable tolerability with no serious adverse events reported. Participants experienced only mild, self-limited injection-site reactions and transient ALT and AST elevations typical of GalNAc-conjugated siRNAs.
RN0361 showed dose-responsive suppression of both ApoC3 and triglycerides through Day 180, with maximum reductions of 93% for ApoC3 and 69% for triglycerides. The therapy also robustly reduced atherogenic lipoproteins, including non-HDL cholesterol, VLDL cholesterol, and remnant cholesterol. Importantly, no changes in fasting glucose or HbA1c were observed versus placebo, indicating the treatment did not adversely affect glucose metabolism.
Addressing Unmet Medical Need
Elevated ApoC3 drives triglyceride-rich lipoprotein accumulation, increasing risks of acute pancreatitis (搜索) and cardiovascular disease (搜索), particularly in patients with diabetes (搜索). Current therapies often fail to achieve sustained control in severe cases, highlighting a significant unmet medical need that RN0361's profound, six-month efficacy from a single dose may address.
"These data confirm RN0361's long-acting potency and favorable safety profile, supporting its advancement in Phase 2 studies in patients with hypertriglyceridemia," said Stella Shi, CEO of Rona Therapeutics (搜索). "By profoundly lowering ApoC3, TG and atherogenic lipids for at least six months after a single dose, RN0361 is an important potential therapeutic for the critical unmet need in severe HTG and CVD risk reduction."
Next Steps
The positive Phase 1 results support RN0361's advancement into Phase 2 studies in patients with hypertriglyceridemia. The data were presented by Dr. Alex DePaoli, MD, Chief Medical Officer at Rona Therapeutics (搜索), marking a significant advance in lipid management for this challenging patient population.
Rona Therapeutics (搜索), founded in 2021, is a global leader in developing next-generation RNAi therapeutics focused on cardiometabolic, obesity, and degenerative diseases. The company has progressed four programs into clinical development leveraging its proprietary platform in delivery, multi-valency, and oligo chemistry, supported by approximately $200 million in funding from global healthcare investors and strategic partners.