Scientists in Canada are claiming a world first, saying that dalcetrapib, a cholesterol drug scrapped by Roche nearly three years ago, could in fact pave the way for a new era of personalised drugs for cardiovascular disease.

In May 2012, a near-16,000 patient Phase III trial of dalcetrapib, a cholesterylester transfer protein (CETP) inhibitor which raises 'good' cholesterol, was stopped due to a lack of clinically meaningful efficacy. Roche then decided to abandon the entire six-trial programme.

However, researchers at the Montreal Heart Institute have revisited the data, which has been published in the Circulation: Cardiovascular Genetics journal, and claimed that it shows patients with cardiovascular disease “and the appropriate genetic background benefit greatly” from dalcetrapib. The team analysed 5,749 patients who received dalcetrapib or placebo and provided a DNA sample.

A “strong association” was discovered between dalcetrapib and a specific gene called ADCY9 (adenylate cyclase 9) on chromosome 16, particularly for a specific genetic variant (rs1967309). In patients with the genetic profile AA at rs1967309, there was a 39% reduction in combined clinical outcomes including heart attacks, strokes, unstable angina, coronary revascularisations and cardiovascular deaths versus placebo. However, in those with genotype GG, there was a 27% increase in events.

A second study, showed that these patients with the favourable genetic profile also benefited from a reduction in the amount of atherosclerosis in their vessels.

Lead investigator Jean-Claude Tardif said the results will lead to “a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalized therapy with dalcetrapib”. He added that “it also offers great hope for precision treatments for patients with cardiovascular diseases and for curbing atherosclerosis, the first cause of mortality in the world”.