A large study of a new type of cholesterol medicine from Merck found it cut the risk of heart attack and death by a modest 9% while causing a build-up of the drug in fat tissue, leaving its commercial future uncertain.
Researchers who presented the findings to a medical congress in Barcelona concluded anacetrapib’s efficacy could be due to its effect on “bad” low-density lipoprotein-cholesterol (LDL-C) rather than any more novel action, Reuters reported.
Merck said it had not decided whether to seek regulatory approval for the treatment—part of a class known as cholesteryl ester transfer protein (CETP) inhibitors designed to raise high-density lipoprotein-cholesterol (HDL-C), the so-called “good” cholesterol.
The company announced in June that the study met its main goal, but details have only now been disclosed. It had also previously said that prolonged use of the drug caused accumulation in fat, which may or may not be a problem.
Bernstein analyst Tim Anderson believes it is now unlikely Merck will decide to file anacetrapib for approval, while Berenberg’s Alistair Campbell described the results as lacklustre. Campbell added, “It is difficult to see overwhelming physician enthusiasm for anacetrapib.”
A little more than a decade ago, CETP inhibitors were hailed as the next big heart drug, but companies including Pfizer, Eli Lilly, and Roche eventually scrapped development programs amid lack of efficacy or safety issues. Since then, drug-makers have gone on to develop and commercialize another class of cholesterol drugs called proprotein convertase subtilisin/kexin type 9, Reuters noted.
Merck presented results from its four-year trial of about 30,000 high-risk heart patients already on statin drugs at the European Society of Cardiology Congress. Statin drugs lower levels of LDL-C.
The study, also published in the New England Journal of Medicine, found that adding anacetrapib to a statin reduced the combined risk of heart attack, heart-related death, and need for repeat artery-clearing procedures to 10.8%, compared with 11.8% for patients on a placebo and a statin. The trial, led by the University of Oxford and funded by Merck, did not find a significant difference in the risk of ischemic stroke.
The researchers noted that anacetrapib raised blood levels of good cholesterol by a mean of 43 mg/dL compared with placebo. The drug also lowered levels of non-HDL-C by 17 mg/dL—a level associated with a 10% reduction in the risk of coronary death or heart attack.
“This result reduces the likelihood that other actions of anacetrapib played a major role in modifying the risk of coronary events,” researchers concluded.
Martin Landray from Oxford, one of the principal investigators, added: "The large increase in HDL cholesterol levels produced by anacetrapib did not appear to have much impact on risk."
Merck said safety data was generally consistent with earlier trials—anacetrapib patients had slightly higher blood pressure levels than the placebo group—but an analysis showed that the experimental drug accumulates in adipose tissue. It found that the amount of anacetrapib in fat tissue fell only a small amount a year after treatment ended. Although animal studies have not indicated harm from this, Merck plans a two-year follow-up of patients to study long-term effects.
Source: Reuters; August 29, 2017.