New study shows investigational BIBF 1120 demonstrated positive trend in reducing lung function loss in Idiopathic Pulmonary Fibrosis

Phase II clinical trial results, published today in the New England Journal of Medicine, for Boehringer Ingelheim’s investigational tyrosine kinase inhibitor (TKI) BIBF 1120* showed a positive trend in reducing lung function decline in patients with idiopathic pulmonary fibrosis (IPF). 1 IPF is a chronic, progressive, severely debilitating lung disease with a high mortality rate, for which there are limited treatment options. 2

In the study, known as TOMORROW (To I mprove Pulm ona ry Fib rosis with BIBF 1120), patients treated with 150 mg of BIBF 1120* twice daily demonstrated a 68 percent reduction in the rate of forced vital capacity (FVC) decline compared to placebo (0.06 litres per year in the BIBF 1120* 150 mg bid arm vs. 0.19 litres per year in the placebo arm). 1 FVC is the volume of air that is expelled into a spirometer following maximum inhalation. FVC decline is a part of the usual examinations conducted in IPF patients. 3 Lung function is scientifically accepted for assessment of treatment effects in IPF patients. 3 Patients treated with 150 mg of BIBF 1120* twice daily also had a lower incidence of acute exacerbations, defined as sudden deterioration of clinical status, compared with placebo. 1 Acute exacerbations are associated with rapid disease progression, severe abrupt decline in FVC and high mortality. 2,4,5

In addition, treatment with 150 mg BIBF 1120* twice daily resulted in a small decrease in the SGRQ score (St George’s Respiratory Questionnaire) as compared with an increase in placebo (-0.66 vs. 5.46; p= 0.007). 1,6 SGRQ scores measure the impact of quality of life, with higher scores – as well as increasing scores – signalling greater impairment. 6

Gastrointestinal symptoms and liver transaminase increases were more frequent in patients receiving 150 mg BIBF 1120* twice daily than placebo; adverse events leading to discontinuation were mostly diarrhoea, nausea and vomiting. 1

“People who suffer from IPF are in great need of a safe and effective treatment to preserve lung function so they can maintain physical activity and reduce the impact on their independence for as long as possible,” said Luca Richeldi, MD, PhD, lead study author and director of the Research Centre for Rare Lung Diseases, University of Modena and Reggio Emilia, Modena, Italy. “The positive trends in slowing the decline in lung function over time, reducing the incidence of acute exacerbations and improving the quality of life with BIBF 1120* are a promising proof of concept.”

BIBF 1120* received orphan-drug designation from the U.S. Food and Drug Administration in June 2011 and by the Ministry of Health, Labour and Welfare of Japan in September 2011, acknowledging the fact that there is a high unmet clinical need for this drug and that it has a high development potential.

“The promising results of the phase II clinical trial for BIBF 1120* in IPF give us the confidence to continue assessing the compound’s potential for improving the lives of patients affected by this very serious disease in phase III clinical trials,” said Professor Klaus Dugi, MD, Corporate Senior Vice President Medicine at Boehringer Ingelheim Headquarters. “With a strong heritage in respiratory medicine, Boehringer Ingelheim remains committed to identifying a safe and effective treatment for IPF to help bridge the unmet therapeutic need for the thousands of people suffering from this fatal disease.”

Two pivotal phase III clinical trials are currently underway enrolling 970 patients in 20 countries. 3,7 The first patients entered the trials in April and May 2011, respectively. 3,7 For more information about the phase III trials or to learn how to enroll, please visit clinicaltrials.gov (identifiers NCT01335464 and NCT01335477). 3,7

References

1. Richeldi L, Costabel U., Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. New England Journal of Medicine September 22, 2011; 365: 1079-1087.
2. Raghu G, Collard H, Egan J, et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med 2011; 183: 788–824, 2011.
3. Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients. Available at: http://clinicaltrials.gov/ct2/show/NCT01335464?term=BIBF+1120&rank=13. Accessed September 2011.
4. Hyzy R, Huang S, Myers J, et al. Acute exacerbation of idiopathic pulmonary fibrosis. Chest 2007; 132(5):1652-1658.
5. Martinez FJ, Safrin S, Weycker D, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005; 142(12 Pt 1):963-967.
6. Jones PW, Quirk FH, Baveystock CM. The St George’s Respiratory Questionnaire. Respir Med September 1991; 85(Suppl B):25-31; discussion 33-7.
7. Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II. Available at: http://clinicaltrials.gov/ct2/show/NCT01335477?term=BIBF+1120&recr=Open&rank=3. Accessed September 2011.
8. Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained recptor blockade and good antitumor efficacy. Cancer Res 2008; 68(12):4774-4782.
9. U.S. National Institutes of Health. Clinicaltrials.gov BIBF 1120. Available at: http://clinicaltrials.gov/ct2/results?term=BIBF+1120.
10. Raghu G, Weycker D, Edelsberg J, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006; 174:810-816.
11. Meltzer EB & Noble PW. Idiopathic pulmonary fibrosis. Orphanet Journal of Rare Diseases 2008; 3:8.
12. Bergeron A, Soler P, et al. Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-b and IL-10. Eur Respir J 2003; 22:69–76.
13. Pulmonary Fibrosis Foundation. What is IPF. 2011. Available at: http://www.pulmonaryfibrosis.org/ipf. Accessed August 2011.
14. Pulmonary Fibrosis Foundation. Symptoms. 2011. Available at: http://www.pulmonaryfibrosis.org/Symptoms. Accessed August 2011.

* BIBF 1120 is an investigational compound. Its safety and efficacy have not yet been fully established.