Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia

Figures & data

Table 1. Current and future TG-lowering agents in clinical trials.

Agent	Target	Phase	TG lowering potency	Important side effects	Reference
Fibrates	PPARα	Approved for HTG	~50%	Gastrointestinal symptoms, increased liver function tests, creatinine rise, myositis
Omega-3 fatty acids	Pleiotropic + liver	Approved adjunctive for CVD risk next to statins	~20%	Gastrointestinal symptoms
Statins	HMG-CoA reductase	Approved	~10–20%	Gastrointestinal symptoms, muscle symptoms
Volanesorsen	ApoC-III (ASO)	EMA: conditional authorization FDA: not approved yet	~70–90%	ISRs, thrombocytopenia	[62,63]
AKCEA-APOCIII-LRx	ApoC-III (GALNac3 ASO)	Phase IIa	~60–80%	Possibly mild ISRs	[66]
Evinacumab	ANGPTL3 (monoclonal antibody)	Phase III	~50%	Not known yet	NCT03452228, NCT03409744
IONIS-ANGPTL3-LRx	ANGPTL3 (ASO)	Phase II	~60%	Not known yet	NCT03371355
ARO-ANG3	ANGPTL3 (siRNA)	Phase IIa	~50–60%	Possibly mild ISRs	NCT03747224

TG, triglycerides; PPARα, peroxisome proliferator-activated receptor alpha; HTG, hypertriglyceridemia; ApoC-III, apolipoprotein C-III; ASO, antisense oligonucleotide; EMA, European Medicines Agency; FDA, U.S. Food and Drug Administration; ISR, injection site reaction; GALNac, N-acetyl galactosamine-conjugated; ANGPTL3, angiopoietin-like 3; siRNA, silencing RNA.

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