Esperion Therapeutics recently announced the launch of Nexlizet (bempedoic acid/ezetimibe) tablets, a new cholesterol-lowering drug, in the US market. On March 30 this year, the company also launched another Nexletol (bempedoic acid) tablet, a new cholesterol-lowering drug in the US market.
Nexletol and Nexlizet are oral, once-daily, non-statin, and low-density lipoprotein cholesterol (LDL) lowering drugs. They were awarded the world's first batch in the United States in February this year. Both drugs have the same indications: as a diet and Adjuvant therapy with a maximum tolerated dose of statins for the treatment of adult patients with heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease that requires further reduction of "bad" cholesterol (LDL-C) levels Adult patients with disease (ASCVD).
These two drugs have a brand new mechanism of action in reducing LDL-C. In particular, Nexletol is the first oral, once-daily, non-statin, cholesterol-lowering (LDL-C) drug that received regulatory approval in the past 20 years. Nexlizet is the first non-statin, cholesterol-lowering (LDL-C) compound drug approved by the regulatory authorities.
In terms of medication, both drugs are recommended: one tablet per day orally, with or without food. Currently, despite receiving standard care (including statins), many patients still fail to meet LDL-C goals. The launch of these two drugs will provide an important treatment option for patients with elevated cardiovascular disease risk due to HeFH and ASCVD patients with elevated LDL-C levels.
LDL-C is a waxy fat-like substance that exists in the human body. Elevated LDL-C promotes the accumulation of LDL-C in the arteries and may cause cardiovascular events, including heart attacks and strokes. Despite receiving standard nursing care, including statin therapy, it is estimated that nearly 15 million patients (about a quarter of patients) in the United States cannot meet the LDL-C level recommended by the guidelines.
Nexletol's active pharmaceutical ingredient is bempedoic acid, which is a first-in-class ATP citrate lyase (ACL) inhibitor that reduces LDL-C by lowering cholesterol biosynthesis and up-regulating LDL receptors. The active pharmaceutical ingredients of Nexlizet are bempedoic acid and ezetimibe (Etimibe), which reduces LDL-C by inhibiting the complementary mechanism of liver cholesterol synthesis and intestinal absorption.
bempedoic acid is a synthetic dicarboxylic acid derivative, which is a prodrug that requires the activation of very long-chain acetyl-CoA synthetase 1 (ACSVL1). Studies have shown that ACSVL1 is lacking in skeletal muscle. Therefore, bempedoic acid is not activated in skeletal muscle, which can avoid statin-related muscle toxicity.
In January 2019, the first three Japanese pharmaceutical companies acquired the commercial rights of two drugs in Europe for US$900 million. In April this year, these two drugs were approved in the EU under the brand names: Nilemdo (bempedoic acid) and Nustendi (bempedoic acid/ezetimibe). In April of this year, Esperion granted exclusive rights to the Japanese pharmaceutical company Otsuka Pharma to develop and commercialize Nexletol (bempedoic acid) and Nexlizet (bempedoic acid/ezetimibe) in Japan.
The approval of Nexletol/Nilemdo and Nexlizet/Nustendi is based on data from the CLEAR clinical trial project. The project was carried out in more than 4000 high-risk and very high-risk patients. The data showed that: (1) when combined with the maximum tolerated dose of statins, Nilemdo/Nexletol significantly reduced LDL-C levels compared to placebo18 %; In patients with statin intolerance, Nexletol significantly reduced LDL-C levels by 28% compared to placebo. (2) When combined with the maximum tolerated dose of statins, Nustendi/Nexlizet reduced LDL-C levels by 38% compared to placebo.
A combined safety analysis conducted in more than 3600 patients confirmed that bempedoic ecid was well tolerated and the overall incidence of adverse events was similar to placebo. Due to the novel and unique mechanism of action, bempedoic ecid will not be activated in skeletal muscle, thus avoiding the occurrence of muscle-related adverse reactions.
The effects of Nexletol/Nilemdo and Nexlizet/Nustendi on cardiovascular disease morbidity and mortality have not been determined. Esperion is conducting CLEAR Outcomes, a global cardiovascular outcome study, and is expected to obtain cardiovascular risk reduction data by 2022.