Comprehensive Report on AD-221 (Atorvastatin 5mg/Ezetimibe 10mg Fixed-Dose Combination)

1. Executive Summary

AD-221, a fixed-dose combination (FDC) of atorvastatin 5mg and ezetimibe 10mg, has emerged as a significant therapeutic option for primary hypercholesterolemia. Developed by Addpharma Co., Ltd. and marketed in South Korea as Atovamibe Tab. 10/5mg by Yuhan Corporation, this FDC leverages the complementary mechanisms of HMG-CoA reductase inhibition by atorvastatin and cholesterol absorption inhibition by ezetimibe. Clinical development, primarily through the Phase 3 trial NCT05131997, has demonstrated that AD-221 achieves superior low-density lipoprotein cholesterol (LDL-C) reduction (approximately 49%) compared to monotherapies with atorvastatin 5mg, ezetimibe 10mg, and even moderate-intensity atorvastatin 10mg. This enhanced efficacy allows a greater proportion of patients to achieve stringent lipid targets. Pharmacokinetic studies indicate that the FDC provides overall systemic exposure comparable to the co-administration of its individual components, despite some variations in peak concentrations for ezetimibe. The safety and tolerability profile of AD-221 is favorable, characterized by a low incidence of adverse events and, notably, no reported cases of myopathy or rhabdomyolysis in its pivotal Phase 3 study. Evidence also suggests a potentially better safety profile, including fewer liver enzyme elevations, compared to moderate-intensity atorvastatin monotherapy. Approved by the South Korean Ministry of Food and Drug Safety in May 2023, AD-221 (Atovamibe) is positioned as a valuable treatment for patients requiring substantial LDL-C lowering, particularly those who may benefit from a lower statin dose to enhance tolerability or for whom moderate-intensity statin monotherapy is insufficient.

2. Introduction

2.1. Context of Hypercholesterolemia and Lipid-Lowering Therapies