Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature

Table 1 Lepodisiran vs olpasiran vs pelacarsen

Feature	Lepodisiran	Olpasiran	Pelacarsen
Type	GalNAc-conjugated small interfering RNA (siRNA)	GalNAc-conjugated siRNA	Antisense oligonucleotide
Target	LPA mRNA (hepatocytes)	LPA mRNA (hepatocytes)	LPA mRNA (hepatocytes)
Mechanism	RNA interference degrades LPA mRNA	RNA interference inhibits apo(a) synthesis	RNase H-mediated degradation of LPA mRNA
Dosing frequency	Twice yearly (biannual)	Every 12-24 weeks depending on dose	Monthly subcutaneous injection
Route	Subcutaneous	Subcutaneous	Subcutaneous
Lp(a) reduction	> 90% reduction sustained for up to 48 weeks	Approximately 90%-95% reduction in phase 2 data	Approximately 80% reduction (dose-dependent)
Duration of action	Long (effects up to 1 year with single dose)	Moderate to long (dose-dependent)	Shorter; Requires regular monthly dosing
Phase of trials	Phase 2 completed; Phase 3 ongoing (ALPINE program)	Phase 2 completed; Phase 3 ongoing [OCEAN(a)-outcomes]	Phase 3 ongoing [Lp(a) HORIZON trial]
Safety profile	Well tolerated; Mild injection-site reactions	Well tolerated; Mild side effects noted	Generally safe; Injection-site reactions, minor flu-like symptoms
Notable advantage	Longest dosing interval	Rapid onset, high potency	Extensive phase 3 data under development

GalNAc: N-acetylgalactosamine; siRNA: Small interfering RNA; mRNA: Message RNA; Lp(a): Lipoprotein(a); apo(a): Apolipoprotein(a).