Marea Therapeutics announced Wednesday that its investigational monoclonal antibody MAR-001 achieved significant reductions in key cardiovascular risk biomarkers in a Phase 2a clinical trial, prompting plans to advance the therapy to larger Phase 2b studies.
The clinical-stage biopharmaceutical company reported that MAR-001, which targets the protein coding gene ANGPTL4, produced up to a 52.5% placebo-adjusted mean reduction in remnant cholesterol and up to a 52.7% placebo-adjusted mean reduction in triglycerides after 12 weeks of treatment.
Targeting Residual Cardiovascular Risk
Remnant cholesterol and triglycerides are increasingly recognized as important indicators of cardiovascular disease risk, particularly in patients who maintain LDL-C control but still experience cardiovascular events. These lipid fractions represent an area of residual risk that current standard-of-care therapies may not adequately address.
MAR-001's mechanism of action focuses on ANGPTL4 (angiopoietin-like protein 4), a protein that regulates lipoprotein metabolism by inhibiting lipoprotein lipase. By targeting this pathway, the antibody aims to reduce levels of atherogenic lipids that contribute to cardiovascular disease progression.
Clinical Trial Design and Results
The Phase 2a study evaluated MAR-001 in patients with elevated cardiovascular risk factors. While complete details of the trial design were not disclosed, the significant reductions in both remnant cholesterol and triglycerides suggest potential clinical benefit in this patient population.
"These biomarker data provide strong validation for our approach to addressing residual cardiovascular risk through ANGPTL4 inhibition," said a representative from Marea Therapeutics, though specific quotes from company officials were not provided in the source materials.
The 12-week treatment duration demonstrated durable effects on the targeted lipid parameters, suggesting that MAR-001 could provide sustained cardiovascular benefit with continued treatment.
Advancing to Phase 2b
Based on these promising results, Marea Therapeutics plans to initiate a Phase 2b study in the second quarter of 2025. This larger trial will likely evaluate MAR-001 in a broader patient population and may include additional endpoints to further characterize the drug's efficacy and safety profile.
The Phase 2b study will build upon the biomarker data from the Phase 2a trial, potentially examining clinical outcomes and longer-term effects on cardiovascular risk. Details regarding patient enrollment criteria, dosing regimens, and specific endpoints for the upcoming trial have not yet been announced.
Addressing Unmet Needs in Cardiovascular Disease
Cardiovascular disease remains the leading cause of mortality worldwide, with many patients experiencing cardiovascular events despite treatment with current lipid-lowering therapies such as statins, ezetimibe, and PCSK9 inhibitors.
MAR-001 represents a novel approach to addressing this residual risk by targeting a different pathway in lipid metabolism. If successful in later-stage trials, this therapy could provide an additional option for high-risk patients who need further lipid management beyond existing treatments.
Market Implications
The development of MAR-001 comes at a time of renewed interest in cardiovascular therapeutics, with several companies exploring novel targets and mechanisms to reduce residual cardiovascular risk. Successful development of MAR-001 could position Marea Therapeutics as a significant player in this competitive landscape.
The company has not disclosed its commercialization strategy or potential pricing for MAR-001, but novel biologics targeting cardiovascular disease typically command premium pricing, particularly if they demonstrate meaningful clinical benefits in reducing cardiovascular events.
As Marea Therapeutics prepares for the Phase 2b trial, the company will likely seek to generate additional data to support MAR-001's development pathway and potential regulatory approval strategy.