Merck & Co’s cardiovascular drug anacetrapib could see a new lease of life after positive results in a phase III trial.
Optimism for the CETP inhibitor had pretty much evaporated after three other drugs in the class – Pfizer’s torcetrapib, Roche’s dalcetrapib and Eli Lilly’s evacetrapib – failed to show a benefit in reducing cardiovascular events when added to statins in patients with elevated cholesterol levels, and in the case of torcetrapib was linked to harm.
Despite those setbacks Merck obstinately ploughed on with developing anacetrapib after carrying out a futility analysis in 2015 on its 30,000-patient REVEAL trial – estimated to have cost upwards of $500m to carry out – and the latest development suggests its faith wasn’t wholly misplaced.
Top-line data from the study suggests that anacetrapib met its primary objective of reducing major coronary events (MACE) – a composite of coronary death, myocardial infarction and coronary revascularisation – compared with placebo in patients at risk for cardiac events already on statin therapy, according to the pharma group.
The safety profile of the CETP inhibitor was also generally consistent with earlier studies of the drug, showing that it accumulates in fat tissue over time, although the implications of that are not clear.
Merck says it will now discuss the data with regulatory authorities to see if it can file for marketing approval, and it will also have to consider the changing market for cholesterol-lowering drugs now that the PCSK9 inhibitors – Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab) – are being used alongside statin therapy.
A final decision on commercialisation will likely depend on the magnitude of the benefit on MACE in REVEAL. Merck’s chief medical officer Roy Baynes told the Goldman Sachs Healthcare Conference earlier this month that there will probably not be a market for the drug if the effect size is small, but a large effect could make the once-daily pill a viable proposition.
For now, that data is under wraps but cardiologists will get a chance to pore over the numbers when REVEAL is presented at the European Society of Cardiology (ESC) 2017 Congress at the end of August in Barcelona, Spain.
Analysts at Jefferies remain cautious on the programme, saying Merck’s careful use of words in its press release “indicates an unclear risk to benefit ratio in our view”.
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 came under assault after the failure of the earlier drugs in the class. Merck’s earlier studies have suggested its drug raises HDL but also lowers LDL and lipoprotein(a), which could stand in its favour.
Merck was not alone when it decided to press on with development of its CETP inhibitor in 2015. Amgen acquired its own candidate AMG 899 in 2015 when it bought Dezima and has advanced it into phase II testing. Another remaining candidate – Bristol-Myers Squibb’s Simcere-partnered BMS-795311 – appears to have been shelved in the interim.