RNA therapeutics
Systematic review of 20 trials and 6,651 patients finds lepodisiran and olpasiran cut apolipoprotein(a) by 75.69% in hyperlipoproteinemia(a) (J Exp Pharmacol 2025)
Original title: Small Interfering RNA (siRNA) in Dyslipidemia: A Systematic Review on Safety and Efficacy of siRNA
This PRISMA-guided systematic review of siRNA therapy for dyslipidaemia pooled 20 studies covering 6,651 participants across four indications. In hypercholesterolaemia, inclisiran reduced LDL by 44.09% and apolipoprotein levels by 37.5%. In hyperlipoproteinemia(a), lepodisiran and olpasiran achieved a 75.69% reduction in apolipoproteins and a 16.25% reduction in LDL. In hypertriglyceridaemia, ARO-APOC3 and plozasiran reduced VLDL and triglycerides by over 50%, and in mixed hyperlipidaemia and chylomicronaemia, plozasiran cut triglycerides by up to 79% and apolipoproteins by 87.5%. The five most common adverse effects across all agents were nasopharyngitis, new-onset or worsening diabetes mellitus, injection site reactions, back pain, and hypertension. The review concludes siRNA therapy's efficacy across dyslipidaemia subtypes, including the Lp(a)-specific agents, outweighs its safety concerns based on current evidence, though long-term data remain needed.
Original abstract
Introduction: RNA interference (RNAi) therapy represents an evolving advancement in the management of dyslipidemia. One prominent form of RNAi therapy is small interfering RNA (siRNA), which has emerged as a promising therapeutic strategy. This study aims to critically analyze the efficacy and safety of siRNA in the treatment of dyslipidemia.
Methods: PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines.
Results: A total of 20 studies with 6651 participants were included in the analysis. The drugs used in the studies were. Inclisiran led to a notable 44.09% reduction in LDL and 37.5% in apolipoprotein levels among individuals with hypercholesterolemia. In hyperlipoproteinemia(a), therapies like Lepodisiran and Olpasiran achieved a 75.69% drop in apolipoproteins and 16.25% in LDL. For hypertriglyceridemia, agents such as ARO-APOC3 and Plozasiran showed over 50% reductions in both VLDL and triglycerides. In mixed hyperlipidemia and chylomicronemia, Plozasiran significantly reduced triglycerides by up to 79% and apolipoproteins by 87.5%. The 5 most common adverse effects reported were nasopharyngitis, diabetes mellitus (including new-onset diabetes mellitus and worsening diabetes mellitus), injection site adverse effects, back pain, and hypertension.
Conclusion: In conclusion, the benefits of siRNA therapy in dyslipidemia management appear to outweigh its potential drawbacks, demonstrating promising efficacy and safety profiles. However, further research is necessary to fully understand its long-term effects and optimize its therapeutic potential.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.