Key result
Subcutaneous SHR-1918 reduces LDL-C by ~59% at 12 weeks in HoFH on stable therapy.
Why the study?
Traditional lipid-lowering therapies rely on residual LDLR function, which is absent or severely impaired in HoFH, whereas ANGPTL3-directed therapies can reduce lipid levels through an LDLR-independent pathway.
Does SHR-1918 reduce LDL-C levels in adults with Homozygous Familial Hypercholesterolemia taking stable lipid-lowering therapy?
Does SHR-1918 reduce LDL-C levels in adults with Homozygous Familial Hypercholesterolemia taking stable lipid-lowering therapy?
SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, substantially reduced LDL-C levels by 59% at 12 weeks in adults with homozygous familial hypercholesterolemia.
LDL-C reductions support ANGPTL3 inhibition in HoFH; leaves open randomized confirmation of outcomes.
Importance Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)–directed therapies could reduce lipid levels through an LDLR-independent pathway. Objective To evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy. Design, Setting, and Participants This was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy. Interventions Patients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up. Main Outcomes and Measures The primary end point was the percent change in serum LDL-C level from baseline to week 12. Results A total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg/dL. At week 12, the mean percent change in LDL-C level was −59.09% (SD, 11.71%; 95% CI, −63.81% to −54.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of −61.32% for homozygous, −56.40% for compound heterozygous, and −72.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1). Conclusions and Relevance Results show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy. Trial Registration ClinicalTrials.gov Identifier: NCT06009393
No takes yet. Share an insight, caveat, or question.
Peng et al. (2026) studied this question. Subcutaneous SHR-1918 reduced LDL-C levels by a mean of 59.09% at 12 weeks in adults with homozygous familial hypercholesterolemia receiving stable lipid-lowering therapy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: