ARRY–502 – CRTh2 Program for Asthma
ARRY-502, an oral CRTh2 antagonist, has the potential to be an effective treatment for patients with asthma, particularly those with severe disease, and may have advantages over competitor molecules in development. In various preclinical models of allergic inflammation, ARRY-502 has demonstrated a high level of anti-inflammatory activity. In a randomized, double blind, 14-day multiple ascending dose Phase 1 trial when ARRY-502 was dosed to healthy subjects, ARRY-502 was well-tolerated at all doses evaluated, with all treatment related adverse events being mild. Dose proportional increases in ARRY-502 exposure were observed with overall low inter subject variability. ARRY-502 provided robust and sustained pharmacodynamic activity in this Phase 1 trial.
Inappropriate inflammatory responses to environmental allergens underlie allergic reactions such as allergic asthma, allergic rhinitis and atopic dermatitis, which collectively affect up to 20% of the United States population. Despite the range of treatments used to treat allergic asthma, there remains a significant need for patients with severe asthma as well as for more convenient, safe and effective therapies for those with mild to moderate persistent asthma. Although severe asthma affects only approximately 10% of the asthmatic population, the condition results in approximately 60% of total healthcare costs associated with asthma. Currently, few treatment options exist for patients with severe asthma.
In severe allergic asthma, there is emerging evidence suggesting that a greater presence of the mediator prostaglandin D2, or PGD2, and an upregulation of CRTh2, the biologically relevant receptor for PGD2-mediated allergic response, that is expressed on inflammatory cells, may play a particularly important role in more pronounced symptoms of asthma such as coughing, difficulty breathing, lower lung function and possibly exacerbations. Activation of CRTh2 has been shown to result in chemotaxis and activation of inflammatory cells and stimulate the production of cytokines that are thought to drive asthma pathophysiology, particularly in the Th2-signature population.
Based on the role of CRTh2 in mediating the actions of PGD2, selective antagonism of CRTh2 presents an attractive therapeutic approach to the treatment of allergic diseases spanning the severity spectrum. In addition, there is a potential for patient selection in allergic asthmatics which would increase the likelihood of successful treatment. There are selective antagonists of CRTh2 in various stages of clinical development with compounds currently being evaluated in Phase 2 studies in allergic rhinitis, asthma and eosinophilic esophagitis.
Development Status: Array is continuing a randomized, double blind, six week, 180 patient, Phase 2 trial in persistent asthma. Array expects top-line results from this trial during the second quarter of calendar 2013 and intends to seek a partner for further development of ARRY-502 in this large market disease.
