Table 4.

Summary of clinical trials targeting APOC-III in various patient populations.

Study	Intervention	Design	Population	Dose	Results
					TG	LDL-C	HDL-C	ApoB	VLDL-C	Non-HDL-C
Witztum et al. [79]	Volanesorsen (ASO)	Phase III Double-blind, placebo-controlled	66 patients with FCS TG >750 mg/dL	Placebo	+18	+6	+7	+4	+15	+7
				300 mg SC	−77	+136	+46	+20	−58	+46
Gouni-Berthold et al. [80]	Volanesorsen (ASO)	Phase III Double-blind, placebo-controlled	114 patients with severe HTG or FCS, TG >500 mg/dL	Placebo 300 mg SC	+1	+5	+4	−2	−12	+1
					−71	+96	+61	+6	−72	−27
Alexander et al. [81]	Olezarsen (ASO)	Phase I/IIa Double-blind, placebo-controlled, single and multiple ascending dose	67 healthy participants with TG ≥90 or ≥200 mg/dL	Placebo	+22	−8	+4	−14	+5	−6
				10 mg SC	−12	+3	+7		−23	−5
				30 mg SC	−11	−7	+19		−2	−6
				60 mg SC	−43	+2	+34		−65	−12
				90 mg SC	−68	+8	+63	−16	−81	−24
				120 mg SC	−77	−7	+62	−26	−68	−26
				Placebo	+18	−1	+3	+3	+6	−1
				15 mg SC QW	−71	−3	+50	−15	−71	−22
				30 mg SC QW	−73	−17	+56	−26	−73	−30
				60 mg SC Q4W	−65	−22	+76	−30	−40	−31
Digenio et al. [88]	Volanesorsen (ASO)	Phase III Double-blind, placebo-controlled	15 patients with T2DM TG 200–500 mg/dL	Placebo	−10	−6	−7	−10	−14	−8
				300 mg SC	−69	0	+42	−21	−73	−22
Clifton et al. [85]	ARO-APOC3 (siRNA)	Phase I Double-blind, placebo-controlled, multiple ascending dose	32 patients with severe HTG (TG ≥300 mg/dL)	Placebo	−19		+9			0
				10 mg SC	−74		+95			−41
				25 mg SC	−92		+116			−60
				50 mg SC	−85		+96			−45
				100 mg SC	−87		+110			−39
			16 patients with chylomicronaemia (TG >880 mg/dL)	50 mg SC	−88		+120			−59
Tardif et al. [91]	Olezarsen (ASO)	Phase II Double-blind, placebo-controlled, dose-ranging	114 patients with moderate HTG and established ASCVD or at high risk of ASCVD (TG 200–500 mg/dL)	10 mg Q4W	−23	+8	+11	0	−27	−6
				15 mg Q2W	−56	−6	+33	−17	−48	−24
				10 mg QW	−60	+16	+40	−7	−56	−15
				50 mg Q4W	−60	+3	+29	−12	−58	−19

ApoB apolipoprotein B, apoC-III apolipoprotein C-III, ASCVD atherosclerotic cardiovascular disease, ASO antisense oligonucleotide, FCS familial chylomicronaemia syndrome, HDL-C high-density lipoprotein cholesterol, HTG hypertriglyceridaemia, LDL-C low-density lipoprotein cholesterol, mAb monoclonal antibody, QW every week, Q2W every 2 weeks, Q4W every 4 weeks, SC subcutaneous, siRNA small interfering RNA, TG triglycerides, T2DM type 2 diabetes mellitus, VLDL-C very-low-density lipoprotein cholesterol