The inhaled PDE4 inhibitor tanimilast shows efficacy in both Th2 and non-Th2 murine models of asthma

Tanimilast is a novel inhaled PDE4 inhibitor currently in phase 3 for the treatment of COPD. PDE4 inhibitors are known to suppress a variety of inflammatory cell functions involved in the pathophysiology of chronic respiratory diseases like asthma and COPD. Moreover, PDE4 inhibitors have shown beneficial effects in preclinical and clinical asthma studies, representing a novel therapeutic option for this disease. This study aimed to evaluate the potential efficacy of inhaled tanimilast as a treatment for severe asthma by using two house dust mite (HDM)-driven mouse models of asthma, one characterised by Th2 and ICS-sensitive inflammation (HDM/Alum) and the other characterised by non-Th2 and ICS-resistant inflammation (HDM/CFA). Moreover, the effect of tanimilast on top of inhaled budesonide was also evaluated in the HDM/Alum model. Eosinophil (EOS) count and cytokines in BALF were used as readouts. Tanimilast dose-dependently reduced EOS in both models reaching a significant effect at 0.3 (42%) and 1 mg/kg (67%) in the HDM/Alum model and maintaining a significant effect (68%, p<0.01 at 3 mg/kg) also in the HDM/CFA model, where budesonide was not effective. This effect was associated with a significant decrease of Th2 as well as Th1 and Th17 cytokines. When tested on top of budesonide, tanimilast at 1mg/kg showed an additional anti-inflammatory effect compared to the steroid or tanimilast alone. Overall, these data demonstrate that tanimilast is able to modulate inflammation alone and in combination with ICS in both Th2 and non-Th2 experimental models of asthma, suggesting a potential therapeutic effect in patients with ICS refractory severe asthma.