Table 1.

Summary of the Results of the Clinical Studies Pertaining to ANGPTL3 Inhibitors

Trial	Design	Intervention	Results
Harada-Shiba M et al32	Double-blind, placebo-controlled, phase 1 randomized clinical trial involving 96 healthy Caucasian and Japanese participants	Evinacumab SC or IV, in 4 different regimens each, versus placebo for 24 weeks.	Similar safety profile of evinacumab and placebo with no serious adverse effects. Similar pharmacokinetic and pharmacodynamic profiles of evinacumab in both ethnicities across all dose regimens. Evinacumab injections produced significant, dose-dependent reductions in LDL-C, TG and ApoB levels both in Japanese and Caucasian subjects.
Gaudet D et al33	Single-group, open-label, proof-of-concept phase 2 study including 9 patients with HoFH on aggressive lipid-lowering regimens	Evinacumab for 4 weeks.	Αt week 4, a mean reduction of LDL-C levels by 49±23%, with an absolute decrease from baseline of 157±90 mg/dl. At week 4, evinacumab reduced ApoB, non-HDL-C, TG and HDL-C levels by a mean of 46±18%, 49±22%, 47% and 36±16%, respectively.
Reeskamp LF et al34	Single-group, open-label clinical trial enrolling 4 patients already participating in the above trial designed by Gaudet et al27	Stable leucine isotope administered and measured in VLDL before and after the administration of evinacumab.	Evinacumab lowered LDL-C by 59±2% and increased IDL-ApoB and LDL-ApoB fractional catabolic rate in all 4 HoFH subjects, by 616±504% and 113±14%, respectively.
Raal FJ et al30	Double-blind, placebo-controlled, phase 3 trial enrolling 60 patients with HoFH on stable lipid-lowering regimen	Evinacumab vs placebo every 4 weeks, for 24 weeks.	In the evinacumab group, reduction of LDL-C levels by an average of 47.1% vs increase of LDL-C levels by 1.9% in the placebo group. Evinacumab reduced LDL-C in both patients with null-null variants and patients with non-null variants, as compared to placebo (−43.4% vs +16.2% and −49.1% vs.-3.8%, respectively). Similar incidence of adverse effects.
Reeskamp LF et al35	2 HoFH patients with null/null LDLR variants on statin, ezetimibe and weekly apheresis, who participated in the aforementioned study of Raal FJ et al29	Coronary computed tomography angiography (CCTA) before randomization and after 6 months of treatment with evinacumab.	Decreased mean pre-apheresis LDL-C levels from 5.51 ± 0.75 and 5.07 ± 1.45 mmol/l to 2.48 ± 0.31 and 2.20 ± 0.13 mmol/l and post-apheresis LDL-C levels from 1.45 ± 0.26 and 1.37 ± 0.39 mmol/l to 0.80 ± 0.16 and 0.78 ± 0.13 mmol/l in patients A and B, respectively. Total plaque volumes reduced by 76% and 85% after 6 months of evinacumab treatment in patients A and B, respectively.
Rosenson RS et al36	Double-blind, placebo-controlled, multicenter, randomized phase 3 trial including 272 patients with refractory hypercholesterolemia (LDL-C≥70mg/dl with atherosclerosis or LDL-C≥100mg/dl without atherosclerosis), resistant to PCSK9 inhibitor and a maximum tolerated dose statin regimen	Evinacumab vs placebo SC or IV until observation at week 16.	At week 16, the differences in the least-squares mean change from baseline in the LDL-C levels between the groups receiving SC evinacumab and placebo ranged from −38.5% to −56.0%, depending on the received dose regimen. The respective differences between the groups receiving IV evinacumab and placebo ranged from −24.2% to −50.5%, depending on the administered dose. Incidence of serious adverse events during the treatment period ranged from 3% to 16%.
Jin M et al37	Meta-analysis of 5 RCTs with a total of 568 subjects	Evinacumab vs placebo.	Evinacumab, as compared with placebo, significantly reduced LDL-C, TG, and HDL-C by 33.123%, 50.959%, and 12.773%, respectively (P < 0.0001 for all comparisons). Incidence of at least 1 treatment emergent adverse event was not significantly different between evinacumab and placebo groups.
ClinicalTrials.gov Identifier: NCT0340974438	Ongoing open-label, single-group, multicenter clinical trial across 12 countries, involving 116 adult and adolescent patients with HoFH	IV administration of Evinacumab for 192 weeks.	The trial will assess the long-term safety and efficacy of evinacumab in patients with HoFH.
ClinicalTrials.gov Identifier: NCT0423391839	Ongoing three-part, single-arm, open-label clinical trial including 20 pediatric participants with HoFH	IV administration of evinacumab in three parts: single IV dose (part A) and IV dose Q4W (parts B and C), up to week 24.	The study will assess the safety, efficacy and pharmacokinetics of evinacumab in pediatric patients with HoFH.