A pre-specified subgroup analysis from the two replicate Phase III INPULSIS trials, presented at the European Respiratory Society International Congress ( ERS ), has shown Nintedanib slowed disease progression in patients with idiopathic pulmonary fibrosis ( IPF ), independent of severity of lung function impairment at baseline.
Idiopathic pulmonary fibrosis is a debilitating and fatal lung disease, with a median survival of 2–3 years after diagnosis. It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing.
The pooled analysis of INPULSIS data looked at annual decline in lung function in two pre-specified groups: baseline forced vital capacity ( FVC ) of greater than 70% ( n=700 ) and less than or equal to 70% predicted ( n=361 ).
The positive effect of Nintedanib on slowing disease progression was similar for both subgroups: • FVC greater than 70% predicted: -111.3mL ( Nintedanib ) vs -220.3mL ( placebo ), difference 109.0 mL ( 95% CI: 68.2, 149.9 ) in favour of Nintedanib; • FVC less than or equal to 70% predicted: -119.7mL ( Nintedanib ) vs -233.2mL ( placebo ), difference 113.5 mL ( 95% CI: 51.3, 175.7 ) in favour of Nintedanib.
The results for both subgroups are consistent with the INPULSIS primary endpoint finding for the overall patient population which showed Nintedanib, one capsule twice a day, slowed disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types - including patients with early disease ( FVC greater than 90% pred ), no honeycombing on HRCT and/or concomitant emphysema.
In a separate, additional analysis of the INPULSIS data, Nintedanib reduced the proportion of patients who experienced disease progression as measured by categorical ( absolute or relative ) FVC decline.
A decline in FVC % predicted of greater than 5% and greater than 10% over 6 or 12 months in patients with idiopathic pulmonary fibrosis is a marker of disease progression and associated with reduced survival.
Results showed: • in both INPULSIS-1 and -2, significantly more patients taking placebo experienced an absolute decline in predicted FVC of greater than 5%, as well as relative declines of greater than 5% and greater than 10% vs Nintedanib; • in INPULSIS-1, significantly more patients in the placebo group experienced an absolute decline in predicted FVC of greater than 10%; the difference in INPULSIS-2 was numerically in favour of Nintedanib but did not reach statistical significance.
In both INPULSIS trials, the most common adverse events were gastrointestinal in nature, of mild or moderate intensity, generally manageable and rarely leading to treatment discontinuation. The proportion of patients with serious adverse events was similar in all groups. ( Xagena )
Source: Boehringer-Ingelheim, 2014