Volanesorsen 285mg/1.5ml solution for injection pre-filled syringes

Abstract Background Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid‐lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta‐analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG. Methods Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022. Results Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: −73.9%; 95%CI: −93.5%, −54.2; p < .001 I 2 = 89.05%; p < .001); VLDL‐C level (MD: −71.0%; 95%CI: −76.6%, −65.4%; p < .001 I 2 = 94.1%; p < .001); Apo‐B48 level (MD: −69.03%; 95%CI: −98.59.4%, −39.47%; p < .001, I 2 = 93.51%; p < .001) and Apo‐CIII level (MD: −80.0%; 95%CI: −97.5%, −62.5; p < .001 I 2 = 94.1%; p < .001) with an increase in HDL‐C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I 2 = 94.34%; p < .001) and in LDL‐C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I 2 = 96.18%; p < .001) without a significant elevation of Apo‐B100 level (MD: +4.58%, 95%CI: −5.64%, +14.79%; p = .380 I 2 = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo‐treated controls. Most of adverse events were mild and related to local injection site reactions. Conclusions In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL‐C, Apo‐B48 and non‐HDL‐C and increment of HDL‐C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.

Abstract licence: CC BY-NC-ND 4.0

AimsNovel drugs that target apoC-III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Olezarsen, a drug similar to its predecessor, volanesorsen, is in Phase 3 trials. A meta-analysis of RCTs was done to study its effect on hypertriglyceridemia.Material and methodsScreening was done on PubMed, Embase, Scopus, and the Cochrane Library from inception to August 2024. We used Review Manager (Version 5.4) for statistical analysis. Subgroups of olezarsen at doses of 10, 50, and 80 mg were made. Continuous outcomes were reported as mean differences with 95% CIs. Adverse events were reported using risk ratios and 95% CIs. The risk of bias was analyzed using the Cochrane risk of bias tool.ResultsFour RCTs with 374 participants, 278 in intervention and 96 placebo controls, were included. At all doses of olezarsen, a significant reduction in fasting triglyceride levels (MD: 45.69; 95% CI: 35.84, 55.54; p p p p = 0.01) were also observed. No significant effect was observed on LDL levels (MD: -0.13; 95% CI: -0.40, 0.14; p = 0.34). Overall, no significant adverse effects were seen compared to placebo (RR: 1.42; 95% CI: 0.66, 3.05; p = 0.37).ConclusionOlezarsen showed remarkable efficacy in lowering triglycerides, with a dose-dependent effect, while significantly increasing HDL levels and reducing apoC-III. Its safety profile is commendable. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large-scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case-to-case basis.

Abstract licence: CC BY