TABLE 1.

PCSK9-related therapeutic approaches in development

Target/Mechanism of Action	Agents in Development	Effects on Lipid Profile	Adverse Events	Notes	References
Monoclonal antibodies	SAR236553/REGN727	Mean LDL-C ↓ 39.6–72.4%	Injection site reactions, leucocytoclastic vasculitis in one patient	REGN727 as add on to atorvastatin in patients with LDL > 100 mg/dl	(101)
		Non-HDL ↓ 33.6–62.5%
		Mean LDL-C ↓ 28.9–67.9%	Injection site reactions, generalized pruritis in one patient	Phase II study with REGN727 as add on to statin with or without ezetimibe	(102)
		Non-HDL ↓ 26.8–57.9%
		ApoB ↓ 20.9–50.2%
		Mean LDL-C ↓ up to 65.4% in single dose studies, ↓ 39.2–62% in multiple dose study as add on to atorvastatin	Elevated levels of serum creatinine kinase	Three phase I studies in healthy volunteers, FH patients, and non-FH hypercholsterolemic patients	(100)
	AMG145	Mean LDL-C ↓ 63–75%	Similar to placebo (incl. injection site hematoma, nasopharingitis, viral upper respiratory tract infection)	Phase Ib study AMG145 as add on to statin therapy	http://www.amgen.com (press release)
		LDL-C ↓ up to 64%	No specific adverse events reported	First in human single-dose study of AMG145 in healthy volunteers	http://circ.ahajournals.org (abstract)
	RN316 / PF-04950615 (iv)	NA	NA		http://www.pfizer.com; http://clinicaltrials.gov
	LGT209	NA	NA		http://www.novartis.com
	1D05-IgG2	LDL ↓ up to 50% in nonhuman primates	NA		(95)
Adnexins	BMS-962476	NA	NA	Currently in preclinical studies. Phase I study is planned to be initiated.	http://clinicaltrials.gov
Small molecule inhibitor	SX-PCSK9	NA	NA		http://www.serometrix.com/
Gene silencing	LNA-ASO: SPC5001	Mean LDL-C ↓ 50% in nonhuman primates	NA	Program discontinued
	siRNA: ALN-PCS	Mean LDL-C ↓ 41%; up to 50%	Rash, no serious adverse events	Results of phase I single dose study in 32 healthy volunteers	http://www.alnylam.com

↓, decrease, NA, not available.