Merck's LIPTRUZET tablets get FDA approval for treatment of elevated LDL cholesterol

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved LIPTRUZET™ (ezetimibe and atorvastatin) tablets for the treatment of elevated low-density lipoprotein (LDL) cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. LIPTRUZET (pronounced LIP-true-zett) contains ezetimibe, an efficacious LDL cholesterol lowering therapy, and atorvastatin, currently one of the most widely prescribed statins in the U.S. Once-daily LIPTRUZET treats two sources of cholesterol by inhibiting both the absorption of cholesterol in the digestive tract - through ezetimibe - and the production of cholesterol in the liver - through atorvastatin.

“A significant percentage of patients are unable to lower their LDL cholesterol to recommended levels despite treatment”

No incremental benefit of LIPTRUZET on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established.

"A significant percentage of patients are unable to lower their LDL cholesterol to recommended levels despite treatment," said Peter H. Jones, M.D., associate professor of medicine, Baylor College of Medicine. "Along with a healthy diet, LIPTRUZET (ezetimibe and atorvastatin) is an effective new lipid-lowering treatment option that may help address this unmet need as the complementary actions of its components can provide significant additional LDL lowering beyond atorvastatin therapy alone."

Indications, contraindications, and selected dosage and administration information

LIPTRUZET is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides and non-high-density lipoprotein cholesterol and to increase high-density lipoprotein (HDL) cholesterol in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. LIPTRUZET (ezetimibe and atorvastatin) is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia (HoFH), as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. No incremental benefit of LIPTRUZET on cardiovascular morbidity and mortality over and above that demonstrated for atorvastatin has been established.

LIPTRUZET is a prescription medicine and should not be taken by anyone who has active liver disease or unexplained persistent elevations in hepatic transaminases or who is hypersensitive to any component of LIPTRUZET. Women who are pregnant, nursing or who may become pregnant should not take LIPTRUZET.

LIPTRUZET is available as a once-daily tablet containing 10 mg of ezetimibe combined with 10, 20, 40, or 80 mg of atorvastatin (LIPTRUZET 10/10, 10/20, 10/40, 10/80 mg, respectively). The dosage range is 10/10 mg/day through 10/80 mg/day.

LIPTRUZET 10/10 and 10/80 mg tablets have been shown to be bioequivalent to coadministration of corresponding doses of ezetimibe and atorvastatin tablets.

LIPTRUZET 10/20 and 10/40 mg tablets have been shown to be clinically equivalent in LDL-C response to the corresponding coadministered doses of ezetimibe and atorvastatin tablets.

The recommended starting dose of LIPTRUZET is 10/10 mg or 10/20 mg taken once-daily, or 10/40 mg once-daily for patients who require a larger reduction in LDL cholesterol (greater than 55 percent). LIPTRUZET can be taken at any time of day, with or without food.

In a clinical study, LIPTRUZET powerfully lowered LDL cholesterol across all doses on average by more than 50 percent (53 to 61 percent, depending on dose)

In a multicenter, double-blind, placebo-controlled clinical study in which 628 patients with hyperlipidemia were treated for up to 12 weeks, LIPTRUZET (co-administered as ezetimibe and atorvastatin) provided LDL cholesterol reductions of 53 percent at the lowest dose (10/10 mg; mean baseline LDL-C 177 mg/dL), 54 percent at the 10/20 mg dose (mean baseline LDL-C 184 mg/dL), 56 percent at the 10/40 mg dose (mean baseline LDL-C 184 mg/dL) and 61 percent at the maximum dose (10/80 mg; mean baseline LDL-C 183 mg/dL). Individualization of drug dosage should be based on therapeutic response.

Pooled across doses, LIPTRUZET reduced LDL cholesterol by a mean 56 percent (mean baseline LDL-C 182 mg/dL) compared with 44 percent for all atorvastatin doses pooled (mean baseline LDL-C 181 mg/dL); p< 0.01. The LDL cholesterol reductions seen by atorvastatin dose were 37 percent at 10 mg (mean baseline LDL-C 185 mg/dL), 42 percent at 20 mg (mean baseline LDL-C 177 mg/dL), 45 percent at 40 mg (mean baseline LDL-C 180 mg/dL) and 54 percent at 80 mg (mean baseline LDL-C 184 mg/dL). The clinical impact of comparative differences in lipid changes between LIPTRUZET (ezetimibe and atorvastatin) and atorvastatin is not known.

In two separate clinical studies, LIPTRUZET 10/40 mg and 10/20 mg provided significantly greater LDL cholesterol reductions and helped more patients get to target LDL cholesterol levels (< 70 mg/dL or < 100 mg/dL) compared to doubling the dose of atorvastatin to 80 mg or 40 mg, respectively

In a six-week study, 556 high risk patients taking atorvastatin 40 mg but not at LDL cholesterol < 70 mg/dL were randomized to either LIPTRUZET 10/40 mg coadministered as ezetimibe and atorvastatin (n = 277; mean baseline LDL-C 89 mg/dL) or atorvastatin 80 mg>

In a separate six-week study, 184 moderately-high risk patients taking atorvastatin 20 mg but not at LDL cholesterol < 100 mg/dL were randomized to either LIPTRUZET 10/20 mg coadministered as ezetimibe and atorvastatin (n = 92; mean baseline LDL-C 120 mg/dL) or atorvastatin 40 mg (n = 92; mean baseline LDL-C 118 mg/dL). Results showed that LIPTRUZET 10/20 mg further lowered LDL cholesterol by an average of 31 percent compared to 11 percent when titrating to atorvastatin 40 mg (p<0.05). This greater additional LDL cholesterol reduction resulted in 84 percent of patients treated with LIPTRUZET 10/20 mg achieving LDL cholesterol <100 mg/dL as compared to 49 percent of patients taking atorvastatin 40 mg.