<![CDATA[<body bgcolor="#FFFFFF" text="#000000">
Incidence
Asthma is a chronic debilitating disease that is rapidly gaining incidence worldwide and the available medications are unable to meet the growing needs.
As it is a chronic ailment, majority of asthma patients require therapy over a long period, sometimes spanning a lifetime.
The global market for asthma medication is estimated at US $ 8-12 billion.
Treatment & Role of PDE-4 Inhibitors
Current medications include inhaled ß- agonists, bronchial steroids and anti-leukotriene antagonists, which target treating asthma by producing anti-inflammatory and/or bronchodialatory effects.
However, none of the existing therapies are able to effectively control the disease and some of the treatments such as steroids have potential side-effects.
Research on PDE-4 inhibitors commenced over the last ten years. The aim is to develop compounds that selectively inhibit Phospodiesterase Enzyme [PDE-4].
PDE-4 is an enzyme that catalyses metabolism of cyclic-AMP, a secondary messenger in cellular functions. Increase in intracellular cAMP levels is known to have both bronchodialatory and anti-inflammatory activities. Hence, selective PDE-4 inhibitors present an attractive alternative for asthma therapy.
However, most PDE-4 inhibitors have exhibited dose limiting side-effects that range from the most common issue of emesis/nausea to cardiac toxicity.
GRC 3886
Glenmark has been researching PDE-4 inhibitors for more than three years which has resulted in a very promising lead candidate GRC 3886.
GRC 3886 is a highly selective PDE-4 inhibitor with no emetic side-effects demonstrated in animal models.
It has excellent in-vitro and in-vivo pharmacological activity against the target.
The compound recently completed Phase I clinical trials in UK [conducted by Quintiles]. Early results of Phase 1 studies have demonstrated that GRC 3886 is well tolerated with predictable pharmacokinetics in human volunteers. Furthermore, the molecule is non-emetic and does not display cardiovascular effects at the highest doses tested in the study.
Additionally, the high TNF-alpha inhibition seen in Phase 1 subjects dosed with GRC 3886 indicates potential for treating Rheumatoid Arthritis [RA]. The company is presently studying preclinical models for validating the use of the compound in RA.
The compound is expected to enter Phase II trials in the US for Asthma and COPD indications in the early part of calendar 2006.
</body>]]>