FDA批准阿托伐他汀/依折麦布复方片剂上市

近日，美国食品与药物管理局（FDA）批准了新型降脂复合片剂Liptruzet（有效成分包括阿托伐他汀和依折麦布）上市，用于和饮食控制一起治疗原发性或混合性高脂血症患者的低密度脂蛋白胆固醇（LDL—C）升高，以及降低纯合子家族性高胆固醇血症（FH）患者的胆固醇水平。该复合片剂每天服用一次，规格包括10mg依泽麦布与10、20、40或80mg阿托伐他汀的组合。

FDA分别于2012和2009年拒绝了该复方片剂的批准。包括辛伐他汀和依折麦布的复合片剂Vytorin已于2002年在美国上市。值得注意的是，生产Vytorin的公司因长期拖延公布ENHANCE研究结果而饱受批评，甚至引起了美国国会委员会的关注。在ENHANCE研究的家族性高胆固醇血症患者人群中，辛伐他汀和依折麦布的联合治疗对于几个替代的影像学终点指标的疗效确实并不优于辛伐他汀单药治疗。

IMPROVE-IT研究纳入了18000例近期发生急性冠脉综合征（ACS）的患者，对比了辛伐他汀40 mg和依折麦布10 mg的联合 与辛伐他汀单药40 mg的疗效，预计今年将有结果。尽管这项研究将有助于阐明加用依折麦布的临床获益，但试验结果是在FDA批准依折麦布作为他汀类辅助药物用于降低胆固醇的近十年之后才公布。

FDA于2012年1月更新了依折麦布/辛伐他汀的处方信息，纳入了SHARP研究数据。该实验显示，与安慰剂相比，复方制剂可更有效地降低慢性肾脏病（CKD）患者的LDL—C水平，降低主要血管事件。然而，因为无法评估依折麦布和辛伐他汀独立贡献，Vytorin的CKD适应证并未获准。

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FDA approves atorvastatin/ezetimibe combo tablet
Dallas, TX - The US Food and Drug Administration (FDA) has approved a new lipid-lowering combination tablet that includes atorvastatin, which went off patent in 2011, and ezetimibe (Zetia, Merck/Schering-Plough) [1]. The combination, known as Liptruzet, is approved for the treatment of elevated LDL-cholesterol levels in patients with primary or mixed hyperlipidemia as an adjunct to dietary changes, as well as for reducing cholesterol levels in patients with homozygous familial hypercholesterolemia (FH).
Liptruzet is available as a once-daily tablet containing 10 mg of ezetimibe combined with 10, 20, 40, or 80 mg of atorvastatin.
The FDA approval is a third-time charm for Merck, the makers of Liptruzet. In 2012, the FDA issued a complete-response letter to the company, stating the agency would not approve the combination tablet and that more data were needed. It also rejected Merck's application for Liptruzet in 2009.
A combination tablet that includes simvastatin and ezetimibe, known as Vytorin, is already available in the US and has been since 2002.
As reported previously by heartwire, both atorvastatin and ezetimibe are very effective at lowering LDL-cholesterol levels, but Vytorin and ezetimibe have been dogged by a lack of hard clinical end-point data. Most notably, the company was criticized for long delays in publishing the ENHANCE study, even attracting the watchful eye of congressional committees in the US. In ENHANCE, a population of patients with familial hypercholesterolemia, the combination of simvastatin and ezetimibe did no better than simvastatin monotherapy on several surrogate imaging end points.
The clinical-outcomes study IMPROVE-IT, which is comparing simvastatin 40 mg plus ezetimibe 10 mg with simvastatin 40 mg alone in 18 000 patients with a recent acute coronary syndrome, is expected to be completed in 2014. Although the study will help clarify the clinical benefit of adding ezetimibe, the trial results will arrive more than a decade after the FDA approved ezetimibe as an adjunct to statins for cholesterol lowering.
In January 2012, the FDA updated the prescribing information for the ezetimibe/simvastatin combination to include data from the SHARP study. In that trial, the combination was shown to more effectively lower LDL-cholesterol levels in chronic kidney disease (CKD) patients, with fewer major vascular events, when compared with placebo. However, a CKD indication for Vytorin was not approved, "because independent contributions of ezetimibe and simvastatin were not assessed."