Despite positive results in a large-scale trial, Merck & Co has decided not to file for approval of its cholesterol drug anacetrapib, saying the data simply isn’t strong enough.
Merck – known as MSD outside North America – made the announcement in a short statement just a few weeks after reporting the results of the REVEAL trial, which involved 30,000 subjects and is estimated to have cost the company around $500m.
It showed that the CETP inhibitor met its primary objective of reducing major coronary events (MACE) – a composite of coronary death, myocardial infarction and coronary revascularisation – reducing it by 9% compared with placebo in patients at risk for cardiac events already on statin therapy after four years.
However, Merck’s drug missed a key secondary objective, failing to reduce a composite outcome of major atherosclerotic events, which could have resulted from a lack of effect on ischaemic stroke, and there was also evidence that anacetrapib accumulates in fat tissue with prolonged dosing, which could raise safety issues.
Some have argued that the company should file given its big investment in the project and established commercial infrastructure, which succeeded in turning another cholesterol-lowering drug with lacklustre data – Zetia (ezetimibe) and sister product Vytorin (ezetimibe plus simvastatin) – into a blockbuster franchise.
However, Merck is adamant that the programme is defunct. “After comprehensive evaluation, we have concluded that the clinical profile for anacetrapib does not support regulatory filings,” said Merck’s R&D chief Roger Perlmutter, adding: “We are deeply grateful to the researchers and patients who participated in the anacetrapib clinical development programme, and in particular the REVEAL outcomes study.”
The drug follows in the footsteps of other CETP inhibitors – including Pfizer’s torcetrapib, Roche’s dalcetrapib and Eli Lilly’s evacetrapib – although those candidates all failed to show a benefit in reducing cardiovascular events when added to statins.
Merck’s decision to abandon the project has no doubt been coloured by the changes to the cholesterol drug market since it started REVEAL several years ago in 2011, when proprietary statins were ruling the roost.
In the interim almost all of those brands have succumbed to generic competition, and new innovative drugs – such as the PCSK9 inhibitors from Amgen and Sanofi/Regeneron – have found it hard breaking into a commoditised category despite stronger effects on cardiovascular outcomes in trials.
CETP inhibitors are designed to increase levels of high-density lipoprotein (HDL) cholesterol – which is sometimes described as ‘good’ cholesterol with a protective cardiovascular effect although that hypothesis has been dented by the CETP class failures.