ESC 2026 LBA | Hengrui Pharma's Innovative SHR-1918 Achieves 64.2% Greater LDL-C Reduction vs. Placebo in HoFH Patients: Phase III Results Unveiled

MUNICH, Germany — In a late-breaking scientific session at the European Society of Cardiology (ESC) Congress 2026, held August 28–31 in Munich, Hengrui Pharma unveiled Phase III results showing its investigational ANGPTL3 inhibitor SHR-1918 achieved a 64.2% greater reduction in low-density lipoprotein cholesterol (LDL-C) compared with placebo in patients with homozygous familial hypercholesterolemia (HoFH).

The multicenter, randomized, double-blind, placebo-controlled trial was led by Professor Peng Daoquan of the Second Xiangya Hospital at Central South University. Professor Peng presented the findings in person during the congress's Late-Breaking Science session, reserved for the most significant cardiovascular research.

A Rare but Deadly Condition

HoFH is a rare genetic disorder caused by severely reduced or absent activity of LDL receptors, leading to extremely elevated LDL-C levels from birth. Without treatment, patients face premature atherosclerotic cardiovascular disease, often experiencing heart attacks in childhood or early adulthood.

"These are among the most challenging patients in lipidology," the researchers noted. "Despite aggressive combination therapy with statins, ezetimibe, and PCSK9 inhibitors, their LDL-C levels remain dangerously high."

SHR-1918, a fully human monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3), offers a novel approach. By inhibiting ANGPTL3, the drug reduces lipid levels through an LDL receptor-independent pathway—potentially bypassing the genetic defect that makes HoFH so difficult to treat.

Study Design and Patient Population

The Phase III trial enrolled 54 HoFH patients aged 12 years and older across multiple centers in China. Participants were randomized 2:1 to receive either SHR-1918 (36 patients) or placebo (18 patients), administered as a 600 mg subcutaneous injection every four weeks.

All patients remained on stable background lipid-lowering therapy throughout the study. The baseline characteristics were well-balanced between groups: mean age was 33.4 years in the treatment group versus 34.6 years in the placebo group. Approximately one-third of patients in each group were homozygous for LDLR mutations (36.1% vs. 44.4%), while the remainder were compound heterozygotes.

Baseline LDL-C levels were markedly elevated—9.8 mmol/L in the SHR-1918 group and 8.6 mmol/L in the placebo group. Notably, all patients were already on statin therapy, more than 90% were taking ezetimibe, and over half were receiving PCSK9 inhibitors, underscoring the refractory nature of this population.

Striking Efficacy Results

At week 12, the primary endpoint results were dramatic. Patients receiving SHR-1918 experienced a 58.8% reduction in LDL-C from baseline, while the placebo group saw a 5.5% increase. The between-group difference of 64.2% was highly statistically significant (95% CI: -74.0 to -54.5; P<0.0001).

In absolute terms, LDL-C decreased by 5.7 mmol/L in the treatment group versus just 0.02 mmol/L in the placebo group, yielding a between-group difference of 5.7 mmol/L (95% CI: -6.8 to -4.6; P<0.0001).

The clinical response was robust: 83.3% of SHR-1918-treated patients (30 of 36) achieved at least a 50% reduction in LDL-C, compared with none in the placebo group.

Importantly, the benefit was consistent regardless of residual LDL receptor function. Both patients with null-null mutations (complete loss of receptor function) and those with non-null mutations showed similar magnitudes of LDL-C reduction, confirming the drug's receptor-independent mechanism of action.

Broad Lipid Benefits

Beyond LDL-C, SHR-1918 demonstrated significant reductions in other atherogenic lipids. At week 12, compared with placebo, the treatment group showed:

• Triglycerides: 54.2% greater reduction

• Apolipoprotein B: 49.0% greater reduction

• Total cholesterol: 59.6% greater reduction

These findings suggest SHR-1918 addresses multiple lipid pathways contributing to cardiovascular risk in HoFH patients.

Sustained Effect at 24 Weeks

Following the 12-week double-blind period, patients in the placebo group crossed over to open-label SHR-1918 treatment. By week 24, both groups showed similar LDL-C reductions: 59.1% in the originally treated group and 54.4% in the crossover group.

The LDL-C target achievement rate at week 24 was 88.9% (32 of 36 patients) in the SHR-1918 group and 66.7% (12 of 18 patients) in the placebo-to-treatment group.

Favorable Safety Profile

SHR-1918 was well tolerated. Adverse events in the treatment group were mostly mild, and no treatment discontinuations occurred. The safety profile during the open-label extension period was consistent with that observed during the double-blind phase.

Regulatory Milestone and Clinical Implications

In February 2026, Hengrui Pharma's new drug application for SHR-1918 was accepted by China's National Medical Products Administration (NMPA) for the treatment of HoFH in adults and adolescents aged 12 years and older.

If approved, SHR-1918 would offer a novel therapeutic option for this ultra-rare population with limited treatment choices. The every-four-weeks dosing schedule, administered via autoinjector, could also improve treatment convenience and adherence compared with more frequent regimens.

"These Phase III results demonstrate that targeting ANGPTL3 represents a promising strategy for HoFH patients who remain at high cardiovascular risk despite maximal conventional therapy," the investigators concluded.

The findings were presented during the Late-Breaking Science session at ESC 2026 in Munich, Germany.