Atopix Therapeutics Ltd has announced the results of a Phase IIb asthma study with their lead compound OC459 at the American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting, San Diego, California, USA on March 1st. (Link to poster: http://www.atopixtherapeutics.co.uk/downloads/atopix-aaaai-poster.pdf)
CRTH2 is a G protein coupled receptor that is selectively expressed by key cell types mediating allergic responses - Th2 lymphocytes, type 2 innate lymphoid cells, basophils and eosinophils. CRTH2 is activated by prostaglandin D2, an abundant lipid product of mast cells.
OC459, a CRTH2 antagonist has previously been shown to reduce airway inflammation and improve lung function in a one month study of allergic asthmatics with moderate persistent disease.
The randomized double-blind study was conducted to determine whether OC459 was effective when dosed at 25 mg or 200mg once daily (OD) and 100 mg twice daily (BD) over three months in a study population containing both allergic and non-allergic asthmatics.
Key findings from the study demonstrated that:
• OC459, at a dose of 25mg once a day, showed a statistically significant improvement in lung function compared to placebo.
• The effect was driven by a responder population of patients with a “Th2 high” eosinophilic phenotype. This group benefited from a large statistically significant improvement in lung function, particularly in those patients under 40 years old where the magnitude of improvement was equivalent to that of high-dose inhaled corticosteroids.
• Treatment with OC459 led to a statistically-significant reduction in the incidence of respiratory tract infections, an effect believed to be due to dampening the harmful Th2 immune response detrimental to the outcome of asthma patients infected with rhinovirus. The effect on respiratory tract infection is important because the majority of asthma exacerbations are precipitated by respiratory viral infection.
The most important factor driving response to OC459 was blood eosinophil count, the biomarker test that Atopix Therapeutics is using in current trials in asthma and other allergic indications.
Tim Edwards, Chairman of Atopix, said: “We are delighted that OC459, our leading oral anti-Th2 therapy, had a clinically meaningful impact in eosinophilic asthma. This highlights the need to stratify patients appropriately to define those most likely to derive optimal clinical benefit. There is a pressing need for a safe oral therapy for eosinophilic asthma which has a positive impact on disease progression and risk of exacerbation, as well as simultaneously treating co-morbid allergic diseases such as allergic rhinoconjunctivitis.”