Table 2.

Summary of antisense oligonucleotide therapy currently available or under investigation.

Target Protein	FDA Approved Therapies	Therapy Under Investigation	Efficacy	Safety
PCSK9	None	AZD8233	ETESIAN phase 2b study: LDL-C and PCSK9 levels were reduced in a dose dependent manner at week 12 for patients on study drug vs. placebo. LDL-C decreased −72% (95% CI −78 to −65) for the 50 mg dose and −79% (95% CI −83 to −74) for the 90 mg dose.	No significant adverse events.
			CV outcomes unknown.	No significant adverse events.
ANGPTL3	None	Vupanorsen	TRANSLATE-TIMI trial: Vupanorsen achieved a decrease in non-HDL-C up to 27.7% in the 80 mg every 2 weeks arm (p < 0.001). Triglycerides were reduced up to 56.8% (p < 0.001) in a dose dependent manner and LDL-C was reduced up to 16% without a dose dependent association.
Lp (a)	None	Pelacarsen	Phase IIb trial: Significant reductions in direct Lp (a) cholesterol in a dose-dependent manner were observed with pelacarsen compared with pooled placebo, by a mean of 29–67% versus 2% respectively, p = 0.001. Pelacarsen was also associated with a modest decrease in laboratory-reported LDL-C.	No significant adverse events.
ApoC3	None	Volanesorsen (approved in EU)	Pooled analysis of four studies showed significant reduction in TG after 3 months of treatment with volanesorsen compared with placebo (MD: −73.9%; 95%CI: −93.5%, −54.2; p < 0.001 I2 = 89.05%; p < 0.001) with significant decrease in LDL-C and increase in HDL-C as well.	Safety concerns related to thrombocytopenia and bleeding.
apoB-100
	Mipomersen
		None
			During phase I, II and III trials, mipomersen significantly lowered LDL-C, apoB-100 and Lp(a) from baseline. In a phase 3 multicenter blinded randomized placebo-controlled study, mipomersen reduced LDL-C by −36.9% as compared to the placebo group at −4.5% (p < 0.001).	Most common side effects include injection site reactions, flu-like symptoms and hepatotoxicity.