DalCor’s Dalcetrapib Demonstrates Genotype-Dependent Effects of Cholesterol Efflux and Inflammation in Data

Effects on C-reactive protein and cholesterol efflux support dalcetrapib benefits on cardiovascular outcomes in patients with AA genotype of ADCY9 gene

Data support the rationale for studying dalcetrapib’s effects on cardiovascular outcomes in DalCor’s ongoing Phase 3 clinical trial in patients with the AA genotype

MONTREAL and LONDON, July 18, 2016 – DalCor Pharmaceuticals and The Montreal Heart Institute today announced the publication in Circulation Cardiovascular Genetics of data demonstrating dalcetrapib’s genotype-dependent effects on high-sensitivity C-reactive protein (hs-CRP) from the prospective analysis of a randomized, placebo controlled clinical trial that included 5243 genotyped patients with acute coronary syndrome (ACS). In addition, cholesterol efflux results support dalcetrapib’s benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309 of the ADCY9 gene from the dal-Plaque-2 clinical study. Cholesterol efflux is a key beneficial component of HDL biology while hs-CRP is associated with deleterious inflammation in the cardiovascular system.

hs-CRP was measured at baseline and end of a 5243 patient study from the dal-OUTCOMES study. The dal-OUTCOMES study was a randomized, double-blind, placebo controlled Phase 3 clinical trial designed to test the safety and cardiovascular efficacy of dalcetrapib in patients with ACS. Cholesterol efflux capacity of HDL from J774 macrophages was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2, a randomized, multicenter, double-blind, placebo-controlled, parallel group Phase 3 clinical trial designed to assess the effect of dalcetrapib on atherosclerotic disease progression in patients with evidence of coronary artery disease. Efflux of HDL from the macrophage using the patient’s blood is a relevant marker of lipid metabolism and is a sign of the healthy positive effect of dalcetrapib in patients with the right genotype.

In the article, titled “Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation: Concordance with Clinical Outcomes” by Jean-Claude Tardif, Marie-Pierre Dubé et al., the authors found that:

  • There was a significant increase in cholesterol efflux in dalcetrapib-treated AA population, but not the GG genotype group;
  • The GG population showed significant increase of hs-CRP whereas the patients with AA genetic profile had no significant increase (and even a trend for a decrease) in hs-CRP when treated with dalcetrapib compared to placebo.


Robert McNeil, Ph.D., chief executive officer of DalCor, said, “Following positive results of the retrospective GWAS study we believe that targeting a genetically specific patient population with dalcetrapib has the potential to reduce risk of cardiovascular events in this select patient population. In this study, four cases of prospective analysis of samples of two different clinical trials delivered expected results: dalcetrapib is beneficial for a select genetic patient group and biology of the response is as we predicted. Consistency of the findings reinforces our expectation that dalcetrapib will show a reduction in clinical cardiovascular outcomes in our ongoing randomized, double-blind, placebo controlled Phase 3 clinical trial evaluating dalcetrapib in patients with the AA genotype. We expect to complete the clinical trial in the first half of 2020.”

Jean-Claude Tardif, C.M., MD, FRCPC, FACC, FAHA, FESC, director of the Research Center at the Montreal Heart Institute and professor of medicine at the Université de Montréal, said, “These data support the hypothesis that patients with a specific genetic profile will respond favorably to dalcetrapib and they provide us with key insight into the biology of this response. Matching dalcetrapib with the right patients based on genotype holds great potential to enhance effectiveness of therapy for better cardiovascular outcomes. This is a major milestone in the battle against atherosclerosis, the leading cause of mortality in the world and we hope to use these findings to further dissect the mode of action of dalcetrapib and potentially improve standard of care for patients with atherosclerotic cardiovascular disease.”

About Dalcetrapib

Dalcetrapib is one of four CETP inhibitors to have reached full-scale development. Over 17,000 patients have participated in dalcetrapib clinical trials. A large, double blind cardiovascular (CV) study, dalOutcomes, randomized over 15,000 patients already taking statins. The drug was well tolerated but the study results were globally neutral – there was no significant reduction in CV events in the dalcetrapib group.

In 2012, investigators at the Montreal Heart Institute led by Professors Jean-Claude Tardif and MariePierre Dubé found a significant association between the effects of dalcetrapib in altering CV events and the polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene. Patients with the AA genotype had a 39% reduction in CV events when treated with dalcetrapib compared to placebo, while GG patients had a 27% increase and AG patients had a neutral effect. This analysis was conducted in 5749 patients. Additional analyses of other studies also demonstrated reduced atherosclerosis in the AA population when treated with dalcetrapib.

DalCor secured a worldwide exclusive license for dalcetrapib together with rights to the genetic marker for use with dalcetrapib and is sponsoring the dal-GenE study, which is planned to include 5,000 patients to prospectively confirm the results of the pharmacogenomic analysis in the dal-Outcomes study in a patient population with the AA genotype at the rs1967309 location in the ADCY9 gene.

About DalCor Pharmaceuticals

DalCor is developing precision treatments by genetically targeting patients that will derive clinical benefits. By integrating clinical and genetic insights, DalCor intends to deliver superior clinical cardiovascular outcomes. The company’s first development program, dalcetrapib, is intended to reduce cardiovascular events in a specific genetic subset of patients. DalCor Pharmaceuticals has offices in Montreal, San Mateo, Calif., Zug, Switzerland and Stockport, U.K. For more information, visit

About the Montreal Heart Institute

Founded in 1954 by Dr. Paul David, the Montreal Heart Institute constantly aims for the highest standards of excellence in the cardiovascular field through its leadership in clinical and basic research, ultra-specialized care, professional training and prevention. It is part of the broad network of health excellence made up of Université de Montréal and its affiliated institutions. The Montreal Heart Institute ranks as the No. 1 research hospital in Canada for research intensity and research funds per researcher, according to Research Infosource. For more information, please visit

DalCor Contacts:

DalCor Pharmaceuticals
Donald Black, M.D.
(609) 613-6637
[email protected]

Russo Partners
Matt Middleman, M.D.
(212) 845-4272
[email protected]

Montreal Heart Institute
Lise Plante
(514) 376-3330 x 2670
[email protected]