Hedgehog pathway inhibitor looks good for idiopathic pulmonary fibrosis

The hedgehog pathway inhibitor taladegib appears to improve outcomes in idiopathic pulmonary fibrosis (IPF) while having an acceptable safety profile, as shown in a phase IIa proof-of-concept trial.

A total of 41 IPF patients older than 40 years who were not receiving concurrent IPF therapy participated in the trial. These patients were randomly assigned to treatment with taladegib at 200 mg (n=21, 86 percent male) or placebo equivalent (n=20, 80 percent male). Treatment was administered orally once daily for 12 weeks, with a 6-week follow-up.

The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy-evaluable population. Measures of fibrosis on high-resolution CT (HRCT) in the efficacy-evaluable population were also evaluated.

All treatment-emergent adverse events (TEAEs) possibly or probably related to the study drug were grade 1 or 2, except one mild or moderate in severity, and none were serious adverse events. The most common TEAEs were dysgeusia (57 percent), muscle spasms (57 percent), and alopecia (52 percent) in the taladegib group; and diarrhoea (20 percent), headache (15 percent), and dizziness (5 percent) in the placebo group.

Compared with placebo, taladegib was associated with a significant improvement in FVC at week 12 (1.9 percent vs –1.3 percent; p=0.035).

Results for multiple HRCT-based measures of disease also favoured the hedgehog pathway inhibitor over placebo. These measures included total lung capacity by HRCT (206.67 vs–55.58 mL; p=0.004) and percent quantitative interstitial lung disease (–9.4 percent vs 1.1 percent; p=0.047). None of the participants died during the trial.