A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients

Abstract

CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late asthmatic response (LAR) to inhaled allergen at screening were randomised to receive CHF6001 400 μg or 1200 μg or placebo administered once a day using a dry powder inhaler. The three treatment periods were 9 days; allergen challenges were performed on day 9 and induced sputum was obtained after 10 h from challenge. Washout periods between treatments were up to 5 weeks. Both CHF6001 doses significantly attenuated the LAR; the primary endpoint analysis showed that CHF6001 400 μg and 1200 μg caused reductions of 19.7% (p = 0.015) and 28.2% (p< 0.001) respectively of the weighted FEV1 AUC4-10h compared with placebo. The difference between the CHF6001 doses was not statistically significant (p = 0.223). Compared with placebo, CHF6001 caused greater reduction in sputum eosinophil counts, although these changes were not statistically significant. CHF6001 was well tolerated, with similar numbers of adverse events in each treatment period. This inhaled PDE4 inhibitor has the potential to provide clinical benefits in patients with atopic asthma.

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

“…A double-blind, placebo-controlled, crossover study showed that compared with placebo, 400 or 1,200 μg of CHF6001 significantly attenuated the late asthmatic response (LAR) and resulted in prominent reduction in sputum eosinophil counts (Singh et al, 2016 ). When topically inhaled by ferrets and rats, no-observed-adverse-effect level dose was extremely lower than those observed for other PDE4 inhibitors (Villetti et al, 2015 ).…”

Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases

“…Allergen challenges were performed on day 9. Both CHF 6001 doses significantly inhibited allergen induced late asthmatic response (Singh et al, 2016). CHF 6001 was well tolerated, with similar numbers of adverse events in each treatment period.…”

“…The recent successful results with CHF 6001, suggest that the systemic biology of PDE4 is less relevant than the lung biology for clinical efficacy in inflammatory respiratory diseases. CHF 6001 is currently the only inhaled PDE4 inhibitor advancing through clinical development and already has promising results in phase II clinical trials in asthma (Singh et al, 2016) and COPD (Singh et al, 2019). The clinical data for CHF 6001 demonstrates anti-inflammatory effects while minimizing the typical PDE4 inhibitor induced systemic side effects.…”

New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma

“…Inhaled PDE4 inhibitors GSK256066 and CHF6001 both inhibit allergen-induced late asthmatic responses 53,54 . An inhaled dual PDE3 and PDE4 inhibitor RPL554 has bronchodilator effects and is well tolerated in patients with asthma 55 .…”