In Mass General Brigham-led phase 2 trial, novel therapy significantly reduced triglyceride levels

A phase 2b clinical trial led byMass General Brigham Heart and Vascular Institute Open external link in a new window researchers shows that a monoclonal antibody therapy called MAR001 can significantly reduce triglyceride levels within 12 weeks for patients with high triglyceride levels. Their results are published in the New England Journal of Medicine Open external link in a new window and were presented simultaneously at the American Heart Association's annual meeting.

"Despite advances in lipid-lowering therapy, many patients continue to have elevated triglyceride levels and cardiovascular risk," says lead author Michelle O'Donoghue, MD, MPH, Open external link in a new window a cardiologist with the Mass General Brigham Heart and Vascular Institute and Senior Investigator in the Thrombolysis in Myocardial Infarction (TIMI) Study Group. "Our findings suggest that MAR001 may be able to safely and effectively lower triglycerides."

Several classes of drugs have been previously shown to lower triglycerides, but MAR001 is novel because it targets ANGPTL4, a protein that naturally inhibits lipoprotein lipase, an enzyme that breaks down triglycerides.

The researchers tested the effectiveness of three different doses of MAR001 in 235 participants with elevated triglyceride levels. Participants were randomly assigned to receive either a placebo or 300, 450, or 900 mg of MAR001 subcutaneously every four weeks for 24 weeks. The trial was designed by the Mass General Brigham Thrombolysis in Myocardial Infarction (TIMI) Study Group with the sponsor Marea Therapeutics, and participants received treatment at 48 centers across the United States, Canada, Australia, and New Zealand.

MAR001 was effective at lowering fasting triglyceride levels and demonstrated a statistically significant, placebo-adjusted reduction in fasting triglyceride levels of 39.1% to 45.5% across three MAR001 dose levels at Week 12. MAR001 treatment was not associated with more frequent adverse effects compared to the placebo.

More research is needed to understand the long-term effects and to assess whether these reductions in triglycerides reduce the risk of pancreatitis and other complications of high triglycerides. In the next phase of the study, the researchers will test MAR001 in participants with severely elevated levels of triglycerides.

"We observed greater reductions in triglycerides in participants with higher baseline triglyceride levels," says O'Donoghue. "We're now evaluating this in a dedicated follow-up study."

Authorship: In addition to O'Donoghue, Mass General Brigham authors include Julia Kuder, KyungAh Im and Marc S. Sabatine. Additional authors include Rebecca A. Juliano, B. Alexander Yi, Bernard Chung, Matilda Hughes, Daniel Gaudet, Harvey White, Gerald F. Watts, Yining Ye, Ethan J. Weiss and Joshua Lehrer-Graiwer, on behalf of the TYDAL-TIMI 78 investigators.

Disclosures: Juliano, Yi, Chung, Hughes, Ye, Weiss and Lehrer-Graiwer are employees of Marea Therapeutics, the study sponsor.

Funding: This research was funded by Marea Therapeutics. Additional disclosures can be found at nejm.org.

Paper cited: O'Donoghue, M. et al., "ANGPTL4 Inhibition in Adults with Elevated Triglycerides." New England Journal of Medicine. DOI: 10.1056/NEJMoa2612463

Contributor

/content/dam/unified-xwalk/cf/providers/3001086

Media contact

Brandon Chase
Senior Specialist, External Communications
[email protected]

About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation's leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.