A fixed-dose combination therapy of obicetrapib plus ezetimibe was found to significantly reduce LDL-C in patients with preexisting or at high risk for developing atherosclerotic cardiovascular disease (ASCVD), according to results from the randomized, double-blind TANDEM trial published May 7 in The Lancet.

Ashish Sarraju, MD, FACC, et al., included 407 participants (median age 68.0 years, 48% women) with preexisiting or high risk of ASCVD or heterozygous familial hypercholesterolemia from 48 centers in the U.S. Trial participants were randomized to one of four groups: obicetrapib 10 mg plus ezetimibe 10 mg fixed-dose combination, obicetrapib 10 mg alone, ezetimibe 10 mg alone or placebo.

The percentage difference in LDL-C reduction when comparing the fixed-dose combination group with placebo at 84 days was –48.6% (95% CI –58.3 to –38.9). For fixed-dose combination vs. monotherapy, the difference was –27.9% (95% CI –37.5 to –18.4) for ezetimibe and –16.8% (95% CI –26.4 to –7.1) for obicetrapib.

Rates of adverse events were similar across treatment groups with the placebo group having the lowest (fixed-dose combination: 52%; obicetrapib alone: 54%; ezetimibe alone 53%; placebo: 37%). A similar trend was observed when analyzing serious adverse events (3%, 6%, 7% and 4%, respectively).

"The [fixed-dose combination therapy] achieved significant [LDL-C] reduction compared with obicetrapib or ezetimibe monotherapy without additional safety concerns, which supports the approach of using initial combination therapy for [LDL-C] lowering rather than the traditional approach of initiating and intensifying monotherapy over time," write the authors.

In an accompanying editorial comment, Seung-Jun Lee, MD, and Byeong-Keuk Kim, MD, PhD, acknowledge the "rigorous, placebo-controlled design" of the trial while also calling out key limitations, such as the study's short duration.

Another recent study, presenting results from the BROADWAY trial, assesses the safety and efficacy of obicetrapib among patients at high risk for cardiovascular events and was published May 7 in the New England Journal of Medicine.

S.J. Nicholls, MB, BS, PhD, et al., randomized 2,530 patients (mean age 65 years, 34% women, mean baseline LDL-C 98 mg/dL) with heterozygous familial hypercholesterolemia or a history of ASCVD and who were receiving maximum tolerated doses of lipid-lowering therapy to either 10 mg of obicetrapib or placebo for 365 days.

Over the year-long study period, the percent change in LDL-C was –29.9% (95% CI –32.1 to –27.8) among those taking obicetrapib, while those taking the placebo had a percent change of 2.7% (95% CI –0.4 to 5.8), resulting in a difference between the two groups of –32.6 percentage points (95% CI –35.8 to –29.5; p<0.001). Additionally, rates of adverse events were similar among the treatment and placebo group.

"The current findings with obicetrapib monotherapy and previous observations regarding obicetrapib in combination with ezetimibe suggest that the addition of obicetrapib to statin therapy can result in more effective treatment of dyslipidemia for many patients," write the authors.