Liptruzet (ezetimibe and atorvastatin) for the Treatment of Hyperlipidaemia, United States of America
Liptruzet (ezetimibe and atorvastatin) is a combination drug indicated to reduce elevated low-density lipoprotein (LDL) cholesterol in patients suffering from hyperlipidaemia disorder. The drug was discovered and developed by Merck.
Merck received approval for Liptruzet from the US Food and Drug Administration (FDA) in May 2013 for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidaemia.
Hyperlipidaemia: disease details
Hyperlipidaemia is a genetic disorder that features abnormally elevated levels of lipids in the blood. The lipids include cholesterol, cholesterol esters, phospholipids and triglycerides. The disease can lead to atherosclerosis and cardiovascular disease, including coronary heart disease.
More than 71 million adult people in the US have high LDL cholesterol, according to Centers for Disease Control and Prevention estimates.
Liptruzet mechanism of action
Liptruzet is a combination of two lipid-reducing drugs: ezetimibe and atorvastatin.
Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine, while atorvastatin reduces the plasma cholesterol and lipoprotein levels by inhibiting LDL production in the liver.
The drug is available for oral administration in doses ranging between 10/10mg/day to 10/80mg/day.
Clinical trials of Liptruzet
The FDA approval for Liptruzet was based on data collected from two six-week and one 12-week Phase III clinical studies.
The 12-week trial was a multicenter, double-blind, placebo-controlled Phase III clinical trial of Liptruzet enrolling 628 patients suffering from hyperlipidaemia.
The study's results demonstrated that the patients treated with Liptruzet showed a 53% reduction of LDL cholesterol at 10/10mg dose, 54% reduction at 10/20mg dose, 56% reduction at 10/40mg dose and 61% at the maximum dose of 10/80mg. The mean reduction of LDL cholesterol in the Liptruzet arm was 56%, while 44% reduction was found in all atorvastatin doses pooled.
Merck's first six-week Phase III clinical trial of Liptruzet enrolled 556 patients with LDL cholesterol. The patients were randomised to receive either Liptruzet 10/40mg co-administered as ezetimibe and atorvastatin, or atorvastatin 80mg.
The results of the study demonstrated that the patients treated with Liptruzet 10/40mg shed LDL cholesterol by an average of 27% when compared to 11% in atorvastatin-administered patients. About 74% of the patients in Liptruzet 10/40mg arm achieved LDL cholesterol of less than 70mg/dL, while just 32% of participants achieved the same in the atorvastatin arm.
Merck's second six-week Phase III trial was conducted on 184 moderately high-risk patients taking atorvastatin 20mg. All the patients had LDL cholesterol at more than 100mg/dL. The patients were randomised to receive either Liptruzet 10/20mg co-administered as ezetimibe and atorvastatin, or atorvastatin 40mg.
Juxtapid (lomitapide) for Treatment of Homozygous Familial Hypercholesterolemia (HoFH), United States of America
Juxtapid (lomitapide) is developed and manufactured by Aegerion Pharmaceuticals for the treatment of patients with homozygous familial hypercholesterolemia (HoFH).
The results of the study showed that the patients treated with Liptruzet 10/20mg lowered LDL cholesterol by an average of 31% when compared to 11% of the patients who were administered with atorvastatin 40mg. The greater additional LDL cholesterol reduction resulted in 84% of the patients in the Liptruzet 10/20mg arm achieving LDL cholesterol, compared to 49% of the patients who achieved it by taking atorvastatin 40mg.
The adverse effects found with the use of Liptruzet during the clinical studies included increased ALT (alanine transaminase), increased AST (aspartate aminotransferase) and musculoskeletal pain.
Marketing Liptruzet in the US
Merck holds the marketing rights of Liptruzet in the US. The drug faces competition from Juxtapid, developed by Aegerion Pharmaceuticals.