Otsuka And Esperion Sign An Exclusive Agreement To Develop Nexletol / Nexlizet In Japan

- Apr 12, 2020-

Japanese pharmaceutical company Otsuka Pharma and U.S. biopharmaceutical company Esperion Therapeutics have recently announced a license agreement. Exclusive rights to Nexlizet (bempedoic acid / ezetimibe).

According to the terms of the agreement, Otsuka will pay Esperion a lump sum of $ 60 million in advance cash. According to the achievement of development and sales goals, Otsuka will also pay a milestone payment of up to $ 450 million, and the net sales of the product in Japan. 15% -30% graded royalties.

This collaboration will advance the commitment of the two companies to provide cost-effective, oral, once-daily, non-statin-based low-density lipoprotein cholesterol reduction (LDL-C, for hypercholesterolemia patients in Japan), Bad cholesterol ") drugs.

Otsuka will be responsible for all development, supervision, and marketing activities in Japan, and will bear all costs related to the development of the Japanese market. Esperion estimates that in the next few years, the total cost of the project will be as high as $ 100 million.

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In February of this year, Nexletol and Nexlizet received the world's first batch of two drugs, both of which are oral, once daily, non-statin, LDL-C lowering drugs, with the same indications: as a diet and maximum tolerated dose Adjuvant therapy with statins for the treatment of adult patients with heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease (ASCVD) that requires further reduction of "bad" cholesterol (LDL-C) levels Adult patients.

It is worth mentioning that Nexletol is the first oral, once-daily, non-statin, cholesterol-lowering (LDL-C) drug that has received regulatory approval in the past 20 years, and Nexlizet is the first non-statin approved by regulatory. 3. The cholesterol-lowering (LDL-C) compound drug has a brand new mechanism of action in reducing LDL-C. 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).

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 standard nursing care, including statin therapy, it is estimated that about one-quarter of patients cannot achieve the LDL-C level recommended by the guidelines.

The active pharmaceutical ingredient of Nexletol / Nilemdo is bempedoic acid, which is a first-in-class ATP citrate lyase (ACL) inhibitor that reduces LDL-C by inhibiting liver cholesterol synthesis. The active pharmaceutical ingredients of Nexlizet / Nustendi are bempedoic acid and ezetimibe (Etimibe), which reduces LDL-C by complementary mechanisms that inhibit liver cholesterol synthesis and inhibit cholesterol intestinal absorption.

bempedoic acid is a synthetic dicarboxylic acid derivative. The drug 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 will not be activated in skeletal muscle, which can avoid statin-related muscle toxicity.

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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 placebo %; 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 is well tolerated and the overall incidence of adverse events is 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.