SHR-1918, a fully human monoclonal antibody targeting angiopoietinlike 3 (ANGPTL3), was associated with a manageable safety profile and substantial reduction in LDL-C in patients with homozygous familiar hypercholesterolemia (HoFH) already taking stable lipid-lowering therapy, according to results of a phase 2 nonrandomized clinical trial published Jan. 7 in JAMA Cardiology.

The single-arm trial enrolled 26 HoFH patients (mean age 36; 62% women; 100% Asian; mean baseline level LDL-C 433.59 mg/dL) across eight sites in China between December 2023 and April 2024. Of the patients, 11 had homozygous, 14 had compound heterozygous and one had double heterozygous HoFH genotype. All were taking lipid-lowering monotherapy or combination therapy, most commonly ezetimibe (96%), rosuvastatin (65%), evolocumab (46%) and/or atorvastatin (35%).

Patients were given subcutaneous injections of 600 mg SHR-1918 every four weeks for 12 weeks.

Results showed a mean LDL-C percentage change of –59% (p<0.001) at the end of the treatment period, with 85% of patients demonstrating a ≥50% LDL-C reduction.

The reduction continued across eight weeks after the final dose and was similar across HoFH genotypes (homozygous –61%; compound heterozygous –56%; double heterozygous –72%). There were also significant reductions in non–HDL-C (–58%), ApoB (–45%), triglycerides (–49%), Lp(a) (–24%), total cholesterol (–56%), HDL-C (–22%) and ApoA1 (–33%).

Study authors Daoquan Peng, MD, et al., call SHR-1918's safety profile favorable, with no severe events or deaths. Among patients, 16 (51.5%) had at least one treatment-emergent adverse event. Most were mild and the most common was proteinuria in four patients (15.4%). One patient had a moderate event (increased alanine aminotransferase, increased aspartate aminotransferase and a urinary tract infection) and one patient had an injection site reaction.

Noting that intravenous evinacumab is the only approved ANGPTL-3 directed therapy for HoFH, Peng et al., write, "intravenous infusion is inconvenient, poses challenges for pediatric patients, and shows risks of infusion-related reactions, phlebitis, and local infections. In contrast, SHR-1918 can be administered subcutaneously."

They add that "the promising findings observed in this trial support the launch of a double-blind, placebo-controlled, phase 3 randomized clinical trial to verify the effect and safety of SHR-1918 for HoFH management."

ANGPTL3-targeting antibodies are just one of the novel therapies discussed in ACC's Familial Hypercholesterolemia: Improving Detection to Accelerate Treatment online course. Access the collection of articles, podcasts and videos for more on FH treatment options, diagnostic criteria, guideline recommendations and strategies for ongoing management.