deCODE provides pipeline update

The company are perhaps best known for its research and development into its first-in-class compound used to treat atherosclerosis for which there is currently no effective drug treatment. deCODE are thought to be the only company that has developed a specific compound to target the product of a gene isolated in a common disease.

The drug candidate, DG041 is a first-in-class small-molecule inhibitor of the EP3 receptor for prostaglandins E2. deCODE identified the EP3 receptor as a drug target through its population genetics research, which has linked variations in the gene, encoding the EP3 receptor to atherosclerosis susceptibility

The company recently completed the single-dose escalation trial of its phase I clinical program for DG041. Results indicated that DG041 was well tolerated at all dose levels tested, no side-effects were detected in the trial, and in particular DG041 did not prolong bleeding time.

The multiple-dose phase I trial of DG041 is currently underway with results expected by late 2005. The very nature of atherosclerosis means that there is a shortage of effective treatment of this disorder, also known as peripheral arterial occlusive disease (PAOD).

This unmet need represents a lucrative opportunity within the market. GlaxoSmithKline are currently looking into the enzyme Lp-PLA2 (lipoprotein-associated phospholipase A2), which researchers hypothesised that the enzymatic action of Lp-PLA2 yielded substances that caused inflammation, so-called inflammatory mediators.

Sankyo's CS-505, a drug developed for the treatment of arteriosclerosis has high expectations placed on it. CS-505 itself is a novel new drug displaying a unique mechanism of action that leads to its status as a first-in-class drug.

deCODE are also involved in an extensive asthma program in which asthma the company has isolated a gene involved in asthma, certain versions of which confer an up to threefold increase in risk of the disease.

Through its population genetics work, deCODE has linked versions of the gene encoding the MAP3K9 kinase with significantly increased risk of asthma. In December last year, deCODE formed an alliance to conduct a phase II clinical trial in asthma of a compound that inhibits this target developed by a third party in another indication.

The randomised, double-blind and placebo-controlled trial began in May and is enrolling 160 asthma patients with the at-risk variants of the gene. The study is examining improvement in lung function and reduction in airway inflammation. The company expects to present results from the trial later this year.

The most effective treatment for asthma is the family of steroids known as glucocorticoids. These drugs are effective in controlling symptoms attributed to airway inflammation, but also have potentially serious side-effects, particularly when administered over a long period of time.

One of the principal goals in the development of new methods for treating asthma is therefore to identify non-steroidal drugs that can effectively control the inflammatory response underlying asthma symptoms.

The company's research and development into therapies for heart attack (myocardial infarction), is done with the knowledge that there are no existing medicines aimed at preventing the pathogenesis of the disease.

In June of this year, deCODE published in JAMA the results of its phase II clinical studies of DG031, its developmental compound for the prevention of heart attack. The results showed that DG031 works to correct a biological perturbation caused by genetic risk factors for heart attack the company has identified, and lowers levels of well established biomarkers for risk of heart attack, including C-reactive protein (CRP) and myeloperoxidase (MPO).

The company is utilising the data gleaned from the phase II program in the design of its phase III clinical outcome study, and is seeking a Special Protocol Assessment from the US Food and Drug Administration (FDA) for the phase III trial. The company expects to begin enrollment for the trial in the fall.

deCODE have also initiated research into gene encoding KChIP1, which is seen as an indication of the disease's presence. The gene also points the way to a potentially powerful new means of stimulating insulin secretion.

In late 2004, deCODE​ and Roche formed a collaboration to co-develop PDE4 inhibitors for the treatment and prevention of vascular diseases, including stroke.

As well as all this, the company has identified three targets involved in obesity, and under its alliance with Merck has advanced one target through high-throughput screening.