What happened
MAR001 enters randomized trial evaluation for adults with elevated triglycerides and remnant cholesterol.
- MD -45.3 percentage points (900 mg); -40.5 percentage points (450 mg); -39.1 percentage points (300 mg)
- P<0.001 for all comparisons
- n=236
Key points
- Context & question: To evaluate the efficacy and safety of MAR001, a monoclonal antibody targeting ANGPTL4, in lowering fasting triglyceride levels in adults with elevated triglycerides and remnant cholesterol.
- Methods & population: Conducted part A of a phase 2b, double-blind, randomized, placebo-controlled trial (NCT07028749) across 236 adults with elevated nonfasting and fasting triglycerides and remnant cholesterol; Participants were randomly assigned (1:1:1:1) to receive subcutaneous MAR001 at doses of 300 mg, 450 mg, or 900 mg, or matching placebo every 4 weeks for 24 weeks; The primary end point was the placebo-adjusted percent change from baseline in fasting triglyceride levels at week 12 in the intention-to-treat population (N=235).
- Finding & limits: At week 12, placebo-adjusted least-squares mean percent changes in fasting triglycerides were -39.1 percentage points for, -40.5 percentage points for, and -45.3 percentage points for. Cardiovascular benefit has not been shown, and the phase 2b results are biomarker data only.
Discussion
Author’s perspective
Michelle L. O’Donoghue6d ago
General · Broad Institute
Look forward to discussion regarding this first-in-class therapy to lower TG by blocking ANGPTL4!
TYDAL-TIMI 78 co-authorExpert perspectives 5
Expert perspective
Michelle O'Donoghue6d ago
The magnitude of triglyceride lowering appeared to be more pronounced among participants with higher baseline levels than among those with lower baseline levels. Treatment did not lead to adverse changes in glucose homeostasis markers or aminotransferase levels or to excess injection-site reactions.
TYDAL-TIMI 78 co-authorExpert perspective
Gurleen Kaur6d ago
In TYDAL-TIMI 78 trial (phase 2b), ANGPLT4 inhibition was effective at ⬇️ triglyceride levels & was not associated w/ more adverse events compared to placebo. Greater reductions in TGs were seen in pts w/ ⬆️ baseline TG levels.
TYDAL-TIMI 78Expert perspective
Mauricio Soto V5d ago
@AHAScience LIVE from #ScientificSessions26 @AHAScience TYDAL-TIMI 78: MAR001, a monthly ANGPTL4 antibody, cut triglycerides 39–46% beyond placebo and remnant cholesterol 37–41%, without worsening glycemia (NEJM). Biomarker data, phase 2b. 4/6
t.coTYDAL-TIMI 78Show 2 more perspectivesShow fewer perspectives
Expert perspective
Martha Gulati6d ago
St.Martha's College Of Nursing
TYDAL-TIMI 78 👥235 adults, high TG ⚖️MAR001 vs placebo 📊12wk: TG ↓39.1–45.5% vs placebo ⚠️Phase 2b: promising lipid signal; CV benefit unproven
TYDAL-TIMI 78Expert perspective
Renuka Jain6d ago
We need longer-term studies in more diverse populations to determine whether these reductions are sustained and to better understand clinical outcomes and the effects of prolonged treatment.
TYDAL-TIMI 78Outstanding questions
Open questions from this trial that would benefit from expert input.
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Full evidence
Why the trial, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, tables, limitations, PICO, abstract, media & sources
Why the trial?
Because angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and regulates triglyceride-rich lipoprotein metabolism, the TYDAL-TIMI 78 trial was conducted to evaluate the anti-ANGPTL4 monoclonal antibody MAR001 for lowering triglyceride levels in adults with elevated triglycerides and remnant cholesterol.
Does ANGPTL4 inhibition with MAR001 reduce fasting triglyceride levels at 12 weeks compared with placebo in adults with elevated triglyceride and remnant cholesterol levels?
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Structured PICO
Does ANGPTL4 inhibition with MAR001 reduce fasting triglyceride levels at 12 weeks compared with placebo in adults with elevated triglyceride and remnant cholesterol levels?
Population
236 adults (mean age 60.4 years, 39% women) with elevated triglycerides (median baseline 249.5 mg/dL; confirmatory fasting TG ≥150 mg/dL and remnant cholesterol ≥30 mg/dL), treated for 24 weeks.
Intervention
MAR001 (monoclonal antibody against ANGPTL4) administered subcutaneously at a dose of 300 mg, 450 mg, or 900 mg every 4 weeks for 24 weeks
Comparator
Matching subcutaneous placebo administered every 4 weeks for 24 weeks
Outcome
Percent change from baseline in fasting triglyceride level at week 12, reported as the difference between each MAR001 dose group and the placebo group (placebo-adjusted change)surrogate endpoint
Main Result
Mean Difference-45.3
p-valuep=<0.001 for all comparisons
In this phase 2b randomized trial (TYDAL-TIMI 78), inhibition of ANGPTL4 with the monoclonal antibody MAR001 produced substantial placebo-adjusted reductions in fasting triglyceride levels of 39.1% to 45.3% at 12 weeks without excess adverse events.
Where experts stand
Lipid management evidence still formingExperts see a strong, well-tolerated triglyceride-lowering signal from a mid-stage trial, but nobody calls it practice-changing because heart benefit is still unproven.
Cardiologists describe the new monthly antibody as clearly effective at lowering triglycerides, with the biggest drops in people who started highest. Early safety looks clean, including no worsening of blood sugar or liver markers. The live question is whether lower triglycerides with this drug will translate into fewer cardiovascular events.
Still unclear
Cardiovascular benefit has not been shown, and the phase 2b results are biomarker data only.
Implication
MAR001 lowers triglycerides via ANGPTL4 inhibition; extends this target as a therapeutic option and supports phase 3 cardiovascular outcome trials.
Abstract
BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and regulates triglyceride-rich lipoprotein metabolism. MAR001 is a monoclonal antibody against ANGPTL4 that is being evaluated for lowering triglyceride levels. METHODS: We conducted a two-part, phase 2b, double-blind, randomized, placebo-controlled trial. In part A, the focus of this report, we enrolled adults who had a nonfasting triglyceride level of at least 175 mg per deciliter and a remnant cholesterol level of at least 35 mg per deciliter at initial screening, followed by a fasting triglyceride level of at least 150 mg per deciliter and a remnant cholesterol level of at least 30 mg per deciliter on confirmatory screening. Participants were randomly assigned in a 1:1:1:1 ratio to receive MAR001 at a dose of 300, 450, or 900 mg or matching placebo subcutaneously every 4 weeks for 24 weeks. The primary end point was the percent change from baseline in the fasting triglyceride level at week 12, reported as the difference between each MAR001 dose group and the placebo group (placebo-adjusted change). RESULTS: A total of 236 participants were enrolled in the trial, with 177 assigned to receive MAR001 and 59 to receive placebo; a total of 235 participants received at least one dose of MAR001 or placebo and were included in the primary efficacy analyses. The mean age of the participants was 60.4 years, and 39% were women. The median triglyceride level at baseline was 249.5 mg per deciliter (interquartile range, 210.0 to 313.0). At week 12, in an intention-to-treat analysis, the placebo-adjusted least-squares mean percent changes in the fasting triglyceride level were -39.1 percentage points, -40.5 percentage points, and -45.3 percentage points for the 300-mg, 450-mg, and 900-mg doses, respectively (P<0.001 for all comparisons). Adverse events occurred in 123 of 177 participants (69%) in the pooled MAR001 group and in 45 of 58 participants (78%) in the placebo group. CONCLUSIONS: Inhibition of ANGPTL4 with MAR001 significantly reduced fasting triglyceride levels at 12 weeks. (Funded by Marea Therapeutics; TYDAL-TIMI 78 ClinicalTrials.gov number, NCT07028749.).
Cite This Study
O’Donoghue et al. (2026) conducted an RCT in Elevated triglyceride levels (n=236). MAR001 (monoclonal antibody against ANGPTL4) vs. Matching placebo was evaluated on Placebo-adjusted percent change from baseline in fasting triglyceride level at week 12 (MD -45.3 percentage points (900 mg); -40.5 percentage points (450 mg); -39.1 percentage points (300 mg), p=<0.001 for all comparisons). MAR001 reduced fasting triglycerides at 12 weeks by placebo-adjusted -39.1, -40.5, and -45.3 percentage points at 300, 450, and doses, respectively.