January 15, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Researchers at the Montreal Heart Institute revisited data from an abandoned Roche clinical trial and may have found strong potential for the drug, dalcetrapib. The Institute announced earlier this week that a team led by Jean-Claude Tardif and Marie-Pierre Dubé had found the drug may, in fact, cause a 39 percent reduction in combined clinical outcomes, including heart attacks, strokes, unstable angina, coronary revascularizations and cardiovascular deaths in the right genetic subgroup.
In May 2012, Swiss-based Roche ended a series of clinical trials on the compound because of lack of clinical efficacy. The Phase III trial had almost 16,000 participants. There were six trials in the program.
The Montreal Heart Institute researchers reanalyzed the data and published the results in the journal Circulation: Cardiovascular Genetics. The researchers analyzed 5,749 patients who received dalcetrapib or placebo and who provided a DNA sample.
The scientists found that individuals with the AA variant of the ADCY9 gene responded better to the drug. The risk of heart attacks, stroke and death were decreased by 39 percent compared to the placebo group. In participants with the GG gene variation, the risk was cut by 27 percent.
“These 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,” said Jean-Claude Tardif, director of the Research Center at the institute and professor of medicine at the University of Montreal in a statement. “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.”
Although too early to know if this study will change the face of personalized medicine, it will likely be identified as a landmark in how important pharmacogenomics is in drug development. Pharmacogenomics is the study of an individual’s unique genetic response to medications.
In the original studies raised the so-called good cholesterol, HDL, by about 30 percent and showed little effect on the so-called “bad” cholesterol, LDL. But there was no observed correlation between the baseline HDL level and clinical outcomes. In the dal-OUTCOMES trials, 15,871 patients with recent acute coronary syndrome were given the drug or a placebo. After a follow-up at around 31 months, the Food and Drug Administration’s Data and Safety Monitoring Board recommended the trial be terminated.
“I think this demonstrates the potential of a personalized medicine approach,” said Scott Heximer of the University of Toronto’s Heart & Stroke Richard Lewar Centre of Excellence for Cardiovascular Research in a statement.
