FDA’s Endocrinologic and Metabolic Drugs Advisory Committee unanimously voted Nov. 2 to recommend Merck’s Vytorin (combination ezetimibe/simvastatin) for use in patients with pre-dialysis chronic kidney disease. However, when it came to whether or not the approval should include patients with end-stage renal disease receiving dialysis, the majority gave a thumbs down.
Whitehouse Station, N.J.-based Merck is seeking approval for Vytorin and for Zetia (ezetimibe) in combination with simvastatin for the reduction of cardiovascular event risk in chronic kidney disease patients. During the committee meeting, FDA members evaluated the results of the SHARP (Study of Heart and Renal Protection) trial.
Currently, ezetimibe is approved as an adjunct to diet for primary hyperlipidemia, homozygous familial hypercholesterolemia and homozygous sitosterolemia. Meanwhile, Vytorin, which contains ezetimibe and simvastatin, is approved as an adjunct to diet for the reduction of elevated total cholesterol and the reduction of elevated total cholesterol and LDL-cholesterol in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments or if such treatments are unavailable. At this time, neither product is approved for use for the aforementioned indication.
The SHARP study was a multicenter, randomized, double-blind, placebo-controlled trial comparing ezetimibe/simvastatin to placebo in the reduction of major vascular events in adults over the age of 40 years with chronic kidney disease with no prior history of MI or coronary revascularization.
While Merck proposed that Vytorin reduced major CV events in chronic kidney disease patients, the company said that the benefit of the drug to reduce CV morbidity and mortality over simvastatin was not yet established. Additionally, the company proposed that while Zetia in combination with simvastatin can reduce CV events in these chronic kidney disease patients, the effect of Zetia alone on CV morbidity and mortality has not been defined.
The SHARP trial, performed at 380 sites in 18 countries, showed that 639 of the 4,193 patients treated with ezetimibe/simvastatin experienced a major vascular event. However, taking ezetimibe/simvastatin reduced the relative risk for a vascular event by 16 percent when compared with placebo.
Meanwhile it was reported that 526 of the 4,650 patients treated with ezetimibe/simvastatin and 619 placebo-treated patients experienced a major atherosclerotic event. However, taking the medication reduced a patient’s relative risk of a major atherosclerotic event by 17 percent when compared with placebo.
Vytorin is available as tablets containing 10 mg of ezetimibe combined with 10, 20, 40, or 80 mg of simvastatin (Vytorin 10/10, 10/20, 10/40, or 10/80 mg, respectively).
While the supplemental new drug applications remain under review, the company said that it expects agency action to occur in the first quarter of 2012.