Exposure‐Efficacy Meta‐Model of Nintedanib in Adult Patients With Chronic Fibrosing Interstitial Lung Diseases

The tyrosine kinase inhibitor, nintedanib, reduces the rate of decline in forced vital capacity (FVC) in a comparable manner in patients with idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis‐associated ILD (SSc‐ILD). The recommended dose of nintedanib in all indications is 150 mg twice daily (BID). Data from Phase II and III trials in IPF, PPF, and SSc‐ILD were incorporated into a meta‐model to holistically investigate the relationship between nintedanib exposure and efficacy. Using data from 2642 patients with IPF, PPF, or SSc‐ILD treated with nintedanib doses ranging from 50 to 150 mg BID, disease progression models with a maximum drug effect on the annual rate of change in absolute FVC (i.e., mL), FVC %predicted, and FVC Z‐score were developed. The estimated plasma concentration producing 50% of the maximum drug effect (EC 50 ) ranged from 6.21 to 10.4 nM (with respect to nintedanib trough concentration) across the explored FVC‐based endpoints. While the disease progression for absolute FVC (mL), FVC %predicted, and FVC Z‐score was different between IPF and PPF patients compared to SSc‐ILD patients, the relative treatment effect of nintedanib, described by a disease‐modifying E max effect, was comparable across indications. The majority of patients achieve exposure levels at or exceeding the EC 50 with the approved starting dose of 150 mg BID.