Novel inhibitory antibody, MAR001, lowers triglycerides and remnant cholesterol in humans

1. ANGPTL4 inhibition decreased triglyceride and remnant cholesterol levels by over 50%.

2. MAR001 was well-tolerated with no significant treatment-related adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: ANGPTL4 is a promising therapeutic target for reducing atherosclerotic cardiovascular disease (ASCVD) risk. While genetic loss-of-function in ANGPTL4 appears safe in humans, prior studies in knockout mice raised concerns about side effects. This randomized controlled trial aimed to evaluate the safety, tolerability, and lipid-lowering effects of MAR001, an ANGPTL4 inhibitory antibody, in healthy individuals and those with metabolic dysfunction. The primary outcome of this study was the safety and tolerability of MAR001, while the key secondary outcome was its impact on triglyceride and cholesterol levels. According to study results, MAR001 reduced triglycerides and remnant cholesterol by over 50% compared to placebo. Although this study was well done, it was limited by its small sample size and short duration, which may not fully capture long-term safety and efficacy.

Click to read the study in The Lancet

Relevant Reading: Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease

In-depth [randomized controlled trial]: Between Nov 20, 2017, and Sept 10, 2019, 56 patients were enrolled in this multi-part study. Included were patients who were either healthy adults, adults with obesity or high triglycerides, or adults with metabolic dysfunction, including type 2 diabetes or insulin resistance with abdominal obesity. Altogether, 55 patients (19 in placebo, 10 in MAR001 150 mg, 9 in MAR001 300 mg, and 17 in MAR001 450 mg) were included in the final analysis. The primary outcome of safety and tolerability showed that MAR001 was generally well tolerated with no significant treatment-related adverse events or inflammatory responses. The secondary outcome of lipid lowering demonstrated that MAR001 at 450 mg led to over 50% reductions in both triglycerides and remnant cholesterol compared to placebo. Overall, findings from this study suggest that ANGPTL4 inhibition with MAR001 is a safe and promising approach to lowering lipid levels in humans.

Image: PD

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