OFEV® (nintedanib)
TOMORROW trial results
Last updated 08.09.2015
These slides are provided by Boehringer Ingelheim for medical to medical education only.
TOMORROW period 1: Randomised, placebo-controlled,
52-week, dose-finding trial
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Endpoints
Primary endpoint:
• Annual rate of decline in FVC
Secondary endpoints:
• Change from baseline to week 52 in SGRQ score
• Incidence of investigator-reported acute exacerbations of IPF
• Time to first investigator-reported acute exacerbation of IPF
• Survival (all cause, respiratory cause)
Safety and tolerability
FVC, forced vital capacity; SGRQ, St George’s Respiratory Questionnaire.
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Inclusion and exclusion criteria
Main inclusion criteria:
Main exclusion criteria:
• ≥40 years
• Medical conditions that might
interfere with participation in study
• Definite or probable IPF diagnosed
according to ATS/ERS criteria2 <5
years prior to screening, and
confirmed by central review of
HRCT performed <12 months prior
to randomization (mandatory) and
surgical lung biopsy (if available)
• FVC ≥50% predicted
• Known risk of bleeding or
thrombosis
• Continuous oxygen
supplementation at randomization
(≥15 hours per day)
• Likely to require lung transplant
during study (investigator’s opinion)
• Single breath DLCO 30–79%
predicted
• Life expectancy for disease other
than IPF <2.5 years (investigator’s
opinion)
• Resting PaO2 ≥55 mmHg (≤1500 m)
or ≥50 mmHg (>1500 m)
• Other investigational therapy
<8 weeks prior to screening
ATS, American Thoracic Society; ERS, European Respiratory Society; HRCT, high-resolution computed tomography.
1. Richeldi L, et al. N Engl J Med 2011;365:1079–1087; 2. ATS and ERS. Am J Respir Crit Care Med 2000;161:646–664.
TOMORROW: Baseline characteristics (1/2)
BMI, body mass index.
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Baseline characteristics (2/2)
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Annual rate of decline in FVC
Difference between nintedanib 150 mg bid and placebo: p=0.064 vs placebo (pre-specified primary multiplicity-corrected
analysis [closed testing procedure]); p=0.014 vs placebo (pre-specified hierarchical testing procedure).
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW:
Preservation of health-related quality of life
*
*p=0.007 vs placebo.
SGRQ, St George’s Respiratory Questionnaire.
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Acute exacerbations
*p=0.02 vs placebo.
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
TOMORROW: Adverse events
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
Conclusions
• Treatment with nintedanib 150 mg bid reduced the annual rate of
decline in FVC by 68% compared with the placebo group
• A reduction in the incidence of acute exacerbations and preservation
of quality of life were observed with nintedanib 150 mg bid versus
placebo
• Nintedanib 150 mg bid had an acceptable safety profile, with a riskbenefit ratio that justified its investigation as a treatment for IPF in the
INPULSIS Phase III trials
Richeldi L, et al. N Engl J Med 2011;365:1079–1087.
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