ELB353: Leveraging PDE platform for chronic inflammatory disorders
About chronic obstructive pulmonary disease, a debilitating inflammatory disorder
Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating respiratory condition that restricts a person’s ability to breathe. COPD is characterized by two major contributing factors: emphysema and chronic bronchitis. In emphysema, the walls between many of the air sacs in the lungs are damaged, which reduces the amount of lung available for vital oxygen exchange. Chronic bronchitis on the other hand is characterized by irritation and infl ammation of the lining of the airways, causing mucus formation and restriction of airfl ow. Both conditions are thought to be caused by heightened infl ammation and can lead to reduced lung function and ultimately to death. According to The World Health Organization, COPD is the fourth most common cause of death; the global prevalence of COPD is rising rapidly and is estimated to affect 80 million people worldwide. The leading cause of COPD is cigarette smoking, although long-term exposure to other lung irritants, such as air pollution, chemical fumes, or dust, may contribute to the disease. There is currently no cure for COPD, although patients are treated symptomatically with bronchodilators and steroids to improve lung function and reduce exacerbations.
ELB353 product profile
ELB353 is an oral phosphodiesterase 4 (PDE4) inhibitor that is being developed as a potential treatment for COPD, but that could also have therapeutic promise in other chronic infl ammatory disorders. PDE4 has been validated as an important infl ammatory signaling target in various pre-clinical and clinical trials.
Biotie believes that ELB353 could be well suited for the treatment of early, aggressive COPD given its convenient oral, once-daily formulation and potential impact on the underlying mechanism of disease. Treating the disease early could help to protect existing, healthy lung tissue and prevent the persistent decline in lung function that is characteristic of this condition. In preclinical testing, ELB353 was a potent disease modifi er in animal models of COPD, asthma, psoriasis, atopic dermatitis, rhinitis, rheumatoid arthritis, and in cigarette smoke-induced lung infl ammation in mice. Importantly, when compared in-vivo to certain other PDE4 inhibitors that are currently in late stage development, ELB353 treatment was very well tolerated with respect to central nervous system and gastrointestinal side effects, which have been a signifi cant development hurdle for PDE4 inhibitors until now.
ELB353 has previously completed one Phase I study in healthy volunteers in which the compound was found to be safe and well tolerated after single and multiple doses of up to 20 mg daily for 10 days. No serious adverse events occurred. The long terminal half life and the pharmacokinetic profi le after multiple dosing suggests that a once daily dosing regimen for this product is feasible.
Clinical trial status
Biotie initiated a Phase Ib placebo controlled, multiple ascending dose study in September 2009 to verify the pharmacodynamic activity, corroborate the safety profile and establish dose ranges to be used in further clinical studies. This study was completed in April 2010. The study evaluated the safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of repeated oral doses of ELB353 in 48 healthy male volunteers. ELB353 was generally well tolerated, and no serious or severe adverse events were reported in any of the study subjects. The pharmacokinetic characteristics of ELB353 demonstrated its suitability for a once daily dosing regimen. Robust and statistically highly significant biomarker responses confirmed the pharmacological activity of well tolerated doses of ELB353 in man.
----
Updated April, 2010