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ARO-DIMER-PA is a Dual-Target RNA Therapy that targets the liver to lower two key proteins involved in high cholesterol at the same time
CHICAGO: A new Cleveland Clinic study shows that a single dose of a gene-silencing medication called ARO-DIMER-PA significantly lowered both "bad" cholesterol (LDL-C) and triglycerides in patients with mixed hyperlipidemia.
The results were presented today during a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2026 in Chicago.
“These results show for the first time that one drug can successfully block two separate disease pathways in the liver at once,” said Luke Laffin, M.D., study author and medical director of the Cleveland Clinic Coordinating Center for Clinical Research in the Heart, Vascular & Thoracic Institute at Cleveland Clinic. “It also reduced other harmful fats (ApoB and remnant cholesterol), suggesting wide-ranging benefits for heart health.”
The drug was generally safe and well-tolerated across the doses evaluated, although the highest dose (400 mg) produced more side effects. The most common side effect was redness at the injection site.
Mixed hyperlipidemia is characterized by high levels of both "bad" cholesterol (LDL-C) and triglyceride-rich fats, both of which increase the risk of heart disease. Current treatment typically requires taking multiple medications to address both conditions.
The medication, ARO-DIMER-PA, is a small interfering RNA. Small interfering RNA (siRNA) is a rapidly expanding group of medications that are administered infrequently with long-lasting results and are well suited to treat chronic cardiovascular disease.
Whereas other siRNA medications for cholesterol only target one gene to silence (PCSK9 or APOC3 separately), this is the first data of a dual-functional siRNA that silences two (both APOC3 and PCSK9) genes with a single medication, while lowering both LDL-C and triglycerides.
The data presented were the phase 1 single-ascending dose component of a randomized, double-blind, placebo-controlled study. Thirty-one patients were randomly assigned to receive a single dose of placebo or one of five doses of ARO-DIMER-PA between 25 and 400 mg.
ARO-DIMER-PA lowered target circulating proteins, PCSK9 and APOC3, by between 50 and 89% and between 43 to 95%, respectively, in a dose-dependent fashion. Similarly, LDL-C and triglycerides were reduced by 26 to 65% and 56 to 78%, respectively, in a dose-dependent fashion.
“These findings support continued evaluation of dual PCSK9/APOC3 inhibition as a potential single-agent strategy for mixed hyperlipidemia,” added Dr. Laffin. “While this study looked at single doses of ARO-DIMER-PA, a separate ongoing study is looking at multiple doses of the medication to help decide correct dose for a pivotal trial. We look forward to assessing optimal dosing, long-term safety, durability and cardiovascular outcomes as a next step.”
The study was funded by Arrowhead Pharmaceuticals.
Dr. Laffin serves on steering committees for Arrowhead Pharmaceuticals, though any compensation is paid to C5Research — Cleveland Clinic Coordinating Center for Clinical Research — Cleveland Clinic's Academic Research Organization.
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation, Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 83,000 employees worldwide are more than 6,600 salaried physicians and researchers, and 21,900 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,725-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, 300 outpatient facilities, including locations in northeast Ohio; Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2025, there were 15.9 million outpatient encounters, 343,000 hospital admissions and observations, and 336,000 surgeries and procedures throughout Cleveland Clinic’s health system. Visit us at clevelandclinic.org. Follow us at x.com/CleClinicNews. News and resources are available at newsroom.clevelandclinic.org.
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