Merck Announces Results of REVEAL Outcomes Study of Anacetrapib, Investigational Medicine for Cardiovascular Disease
KENILWORTH, N.J.--(BUSINESS WIRE) August 29, 2017 --Merck (NYSE:MRK), known as MSD outside the U.S. and Canada, and researchers in the Clinical Trial Service Unit at the University of Oxford, today announced the publication and presentation of results from the REVEAL (Randomized EValuation of the Effects of Anacetrapib through Lipid modification) outcomes study of anacetrapib, Merck’s investigational cholesteryl ester transfer protein (CETP) inhibitor. In the study of 30,449 patients with atherosclerotic vascular disease receiving LDL-C lowering treatment with atorvastatin, anacetrapib significantly reduced the risk of major coronary events (composite of coronary death, myocardial infarction or coronary revascularization) by 9 percent relative to placebo (10.8% vs. 11.8%, respectively; P=0.004). The safety of anacetrapib was generally consistent with data from earlier trials of the drug. However, a sub-study also showed that anacetrapib accumulates in adipose tissue with prolonged dosing. Merck is reviewing the results of the trial with external experts and will consider whether to file new drug applications with the U.S. Food and Drug Administration (FDA) and other regulatory agencies.
The results of REVEAL were presented today by Dr. Martin Landray of the University of Oxford, the trial’s co-principal investigator, during a late-breaking clinical trials session at the European Society of Cardiology Congress, and simultaneously published in the online edition of The New England Journal of Medicine. REVEAL was designed and independently conducted by investigators at the Clinical Trial Service Unit at the University of Oxford, the trial’s regulatory sponsor, in collaboration with the TIMI Study Group based at Brigham and Women’s Hospital in Boston and Merck. Merck provided funding for REVEAL.
“Despite treatment advances in recent years, patients with cardiovascular disease remain at risk for cardiovascular events. We are pleased that adding anacetrapib to statin therapy resulted in a further reduction of major coronary events in REVEAL,” said Dr. Roy Baynes, senior vice president, head of clinical development, and chief medical officer, Merck Research Laboratories. “This trial helps to advance our understanding of the effects of anacetrapib on cardiovascular risk, and we are grateful to the study leaders at Oxford, TIMI, the many investigators, and the thousands of patients who participated in this study for their efforts.”
In the randomized, double-blind, placebo-controlled study, 30,449 adults with atherosclerotic vascular disease on study-mandated intensive atorvastatin therapy (mean baseline LDL cholesterol level 61 mg/dL [1.58 mmol/L], non-HDL cholesterol 92 mg/dL [2.38 mmol/L], and HDL cholesterol 40 mg/dL [1.03 mg/dL]) were randomly assigned to receive either anacetrapib 100 mg once daily or matching placebo. The primary assessment was an intention-to-treat comparison among all randomized participants of the effect of anacetrapib on the composite of major coronary events, defined as the first occurrence of coronary death, myocardial infarction, or coronary revascularization.
Compared with placebo, the addition of anacetrapib further reduced the mean level of non-HDL cholesterol by 17 mg/dL (0.44 mmol/L,18%) and increased HDL cholesterol level by 43 mg/dL (1.12 mmol/L, 104%) at the study midpoint. During median follow-up of 4.1 years, a 9 percent relative reduction in the risk major coronary events was observed among those receiving anacetrapib compared to placebo (1640 events [10.8%] vs. 1803 events [11.8%]; rate ratio 0.91; 95% CI 0.85 to 0.97; P=0.004). The benefit was similar across multiple pre-specified subgroups.
The difference in the key secondary composite outcome of major atherosclerotic events (myocardial infarction, coronary death or presumed ischemic stroke) did not reach statistical significance (rate ratio, 0.93; 95% CI, 0.86 to 1.00; P=0.052), possibly due to a lack of observed benefit of anacetrapib on presumed ischemic stroke. There were no statistically significant differences in cause-specific mortality, cancer, or other serious adverse events. Anacetrapib produced small increases in systolic and diastolic blood pressures of 0.7 mmHg and 0.3 mmHg, respectively; there was no statistically significant increase of serious adverse events attributed to hypertension. Compared to those receiving placebo, more patients in the anacetrapib group developed an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 by the end of the study (11.5% vs. 10.6%; P=0.04); there was no statistically significant impact on the development of albuminuria or serious adverse events attributed to renal failure.
Details on the REVEAL study design are available at clinicaltrials.gov: https://clinicaltrials.gov/show/NCT01252953.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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Posted: August 2017