Audacious DalCor to Develop Roche's Abandoned Dalcetrapib


dalcor_logoDalCor Pharmaceuticals, a London based one year old company made an audacious move and announced that they will continue the development of Hoffmann–La Roche‘s discarded cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib.

Dalcetrapib or JTT-705 structureDalCor Pharmaceuticals has announced that they will continue the development of dalcetrapib or JTT-705, development of which was discontinued by Roche in May 2012. This comes as a result of the completion of a private financing of $150 million. DalCor had closed a $50 million series A financing round in 2015 and now did a $100 million series B this week. DalCor has already started to recruit 5000 patients that were diagnosed by using Roche’s diagnostic tests. The investors in DalCor are Sanderling Ventures and André Desmarais including new investors Caisse de depot et placement du Quebec, the Fonds de solidarite FTQ and CTI Life Sciences Fund. Additionally, undiscovered investors also participated.

how dalcetrapib works

Figure 1. How dalcetrapib works in cardiovascular diseases? (Photo credit: Shinkai H, Vasc Health Risk Manag. 2012;8:323-31. doi: 10.2147/VHRM.S25238.)

CETP inhibitors are designed to reduce the risk of cardiovascular diseases like atherosclerosis. These inhibitors work by improving blood lipid levels, increasing high-density lipoproteins (HDL, good cholesterol) and decreasing low-density lipoproteins (LDL, bad cholesterol). Dalcetrapib is one of the four CETP inhibitors to have reached full scale development.

A double blind cardiovascular study was conducted by Roche with over 15000 patients who were administered dalcetrapib. The study results showed that while the drug was well tolerated, there was no significant reduction in the cardiovascular events on the dalcetrapib group and the dalcetrapib development programme was terminated. Later in 2012, researchers at the Montreal Heart Institute revealed a significant association between the effects of dalcetrapib in altering cardiovascular events and the allelic polymorphism at the rs1967309 location in the adenylate cyclase type 9 gene. The following results were noted:

  • Patients with AA polymorphism had 39% decline in CV events
  • Patients with GG polymorphism had 27% increase in CV events
  • Patients with GA polymorphism showed neutral effects

The results were corroborated in a subsequent analysis of 386 patients from dalcetrapib plaque study, which measured changes in carotid intima media thickness (cIMT). Patients with AA allele showed regression in cIMT while those with GG allele progressed.

DalCor recently got a worldwide license for dalcetrapib. DalCor shall sponsor the dalGenE study which is planned to include 5000 patients to confirm the results of the dalcetrapib outcomes in patients with AA polymorphism.

Robert McNeil, Ph.D., chief executive officer of DalCor, said, “This trial represents a major step forward in cardiovascular medicine, opening new doors and creating therapeutic options for patients of specific genetic composition suffering from heart disease. We believe that targeting a genetically specific patient population with dalcetrapib has the potential to dramatically reduce cardiovascular risk in this select patient population and will demonstrate the long expected benefit of CETP inhibitors. DalCor and its investors are committed to developing dalcetrapib as the first precision medicine for cardiovascular treatment personalized for patients with a specific genetic profile.”

It is worth mentioning here that recently Eli Lilly concluded from its study that evacitrapib, a CETP inhibitor, though maintained the blood lipid levels but did not decrease the risks of cardiovascular diseases. Pfizer and Roche also had to face similar failures. Well, at this moment, we can only wish DalCor a success with dalcetrapib!

Featured image credit: Artery Disease © digitalista (Stock Photo ID: 96386159)

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