Lipoprotein(a) in clinical practice: From genetic risk assessment to therapeutic silencing

Table 2 Estimated lipoprotein(a) reduction, development stage, and safety of small interfering RNA and antisense oligonucleotide therapies

Therapy	Estimated Lp(a) reduction	Development stage	Safety	Ref.
Inclisiran (siRNA)	-13.5% to -26% (modest and variable reduction)	Approved for LDL-C; Lp(a) effect evaluated in ORION studies	Well tolerated; main adverse events: Mild injection-site reactions	Ray et al[110], Ray et al[111], Raal et al[113], Ray et al[126], Wright et al[130]
Olpasiran (siRNA)	> 95%	Phase 3 ongoing	Favorable profile; mild local reactions and transient flu-like symptoms	Rosenson et al[131], Nurmohamed et al[132], O'Donoghue et al[133], Tweneboah et al[134], Lampsas et al[137], Fazoli et al[141]
Zerlasiran/SLN360 (siRNA)	96%-98%	Phase 1	Good initial tolerability; mild injection-site reactions	Nissen et al[142], Rider et al[143], Nair et al[144]
Lepodisiran (siRNA)	> 90% (prolonged effect, up to 1 year)	Phase 1/2	Predominantly mild and transient adverse events	Nissen et al[145], Nissen et al[146], Tsimikas[159]
Pelacarsen (ASO)	-77% to -80%	Phase 3 ongoing	Favorable profile; mainly mild/moderate injection-site reactions	Bhatia et al[147], Hardy et al[152], Tsimikas et al[153], Yu et al[154], Viney et al[155], Susan-Resiga et al[156], Cho et al[157], Parhofer et al[158]

Lp(a): Lipoprotein(a); siRNA: Small interfering RNA; ASO: Antisense oligonucleotide; LDL-C: Low-density lipoprotein cholesterol.