- DalCor secured a world-wide exclusive license from Roche for dalcetrapib together with rights to the genetic marker for use with dalcetrapib
- DalCor will sponsor the Dal-GenE study, which is planned to include 5,000 patients to prospectively confirm the results of the dal-Outcomes study
- The study was initiated in the first half of 2016, and will be performed in 33 countries.
DalCor Pharmaceuticals was formed in 2015 with the initial purpose of confirming the findings of a pharmacogenomics analysis done in the dal-Outcomes study showing that ACS patients having an AA polymorphism at the rs1967309 location in the ADCY9 gene have significantly fewer cardio vascular events when treated with dalcetrapib, a CETP inhibitor, than with placebo.
Heart disease remains the principal cause of death in the world and the incidence has increased in each of the last 60 years. Despite the widespread utilization of statins, and the overall reduction in serum cholesterol, one in four people will die of ischemic heart disease or stroke globally.
Cholesterol Ester Transfer Protein (CETP) inhibitors have been developed following the recognition of an association of CETP polymorphisms and changes in HDL-c in Japan.
Dalcetrapib (originally developed by Japan Tobacco, Roche) is one of four CETP inhibitors to have reached full-scale development. Others are torcetrapib (Pfizer), anacetrapib (Merck) and evacetrapib (Eli Lilly). Over 17,000 patients have participated in dalcetrapib clinical trials with more than 10,000 having received dalcetrapib. A large, double blind cardiovascular (CV) study, dal-Outcomes, randomized over 15,000 patients already taking statins for cholesterol control. However, the study results were equivocal—while the drug was well tolerated, there was no significant reduction in CV events in the dalcetrapib group, and the dalcetrapib development program was terminated.
In 2012, investigators at the Montreal Heart Institute lead by Prof. Jean-Claude Tardif and Marie-Pierre Dube found a significant association between the effects of dalcetrapib in altering CV events and the allelic polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene. Patients with an AA polymorphism had a 39% decline in CV events (dalcetrapib compared to placebo), while GG had a 27% increase, and GA had a neutral effect, in the cohort of dal-Outcomes patients. This retrospective analysis was conducted in 5,749 patients. These results were corroborated in a subsequent retrospective analysis of 386 patients from the dal-Plaque study, which measured change in carotid intima-media thickness (cIMT). Patients with an AA allele showed regression in cIMT, while patients with GG progressed.
A finding of a drug-by-gene interaction for a large at-risk population, not related to drug metabolism, is unique and unexpected. Additionally, the amount of CV event reduction demonstrated on top of statins is commensurate with the benefits seen with high-dose statin compared to placebo. The ability to provide precise, genome-directed medical intervention, with a low number-needed-to-treat (NNT) is a new paradigm in the care of life-threatening vascular disease. Roche, as the sponsor of this retrospective study, filed patents covering this genetic marker for use with dalcetrapib and other CETP inhibitors. These patents extend to 2034.
DalCor recently secured a worldwide exclusive license for dalcetrapib together with rights to the genetic marker for use with dalcetrapib and other CETP inhibitors and will sponsor the dal-GenE study, which is planned to include 5,000 patients to prospectively confirm the results of the pharmacogenomics analysis in the dal-Outcomes study in a patient population having an AA polymorphism at the rs1967309 location in the ADCY9 gene. The study was initiated in the 1st half of 2016, and will be performed in 33 countries.
For additional information about the dal-GenE study please visit clinicaltrials.gov and access NCT02525939.