Patients aged at least 40 years with a predefined IPF diagnosis of less than 5 years prior to the study screening were included in the study. Eligible patients had a FVC≥50% and a DLCOpred 30-79% and a PaO2 ≥55mmHg. Concomitant oral therapy with prednisone (or equivalents) of ≤15 mg if stable during the 8 weeks previous to the study enrollment.
The primary efficacy endpoint was represented by the FVC decline rate and the secondary endpoints included changes from baseline in FVC, DLco, SpO2, TLC, exercise capacity, SGRQ (St. George respiratory questionnaire) scores, the incidence of acute exacerbations, overall mortality, and that due to respiratory causes.
The highest BIBF 1120 dose was associated with the most significant therapeutic effect on the lung function decline compared to placebo, the drug reducing the annual rate of lung function decline by 68.4% compared to placebo group.
The highest dose of BIBF 1120 therapy was also associated with a lower percentage of patients exhibiting a significant reduction of the FVC (of >10% or of >200ml) compared to placebo (23.8% versus 44%, p=0.004). Unlike placebo BIBF 1120 preserved the total lung capacity (−0.24 liters vs. 0.12 liters, p<0.001).
Mean change from baseline in the SpO2 was −0.2% with BIBF 1120 and −1.3% with placebo (p = 0.02). The highest dose therapy was also associated with a lower percentage of significant desaturation (>4% reduction from baseline in resting SpO2) over the study period 3.6% respectively 11.0%, p = 0.03). BIBF 1120 didn’t exert a significant therapeutic benefit on the DLCO and in the exercise capacity as compared to placebo.
Health Related Quality-of-Life (HRQoL) evaluated with SGRQ was found to be significantly improved with the BIBF highest dose as compared to placebo the difference being also clinically significant: mean change −0.66 points with the active treatment compared to 5.46 points with placebo p = 0.007.
Overall, there were comparable incidences of adverse events among all groups with comparable rates of severe/life-threatening effects as well. The adverse events which most commonly led to treatment discontinuation were diarrhea, nausea, and vomiting and were reported in the group receiving 150 mg twice a day.
The TOMORROW trial is planned to be followed by an open-label continuation phase in which efficacy and safety of BIBF-1120 are planned to be further studied.
Two phase III studies aimed at evaluating the efficacy and safety of BIBF 1120 150 mg×2/day over 52 weeks in patients with IPF are also planned. These two studies have similar endpoints which include the annual decline rate in FVC, quality of life and time to first exacerbation, overall survival.