Dr Heike Specht
Binger Strasse 173
Results from Phase II TOMORROW trial with BIBF 1120* also presented at European Respiratory Society (ERS) 2011 Annual Congress
For NON-U.S Health Media Only
Ingelheim, Germany, 22 September 2011 – 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 Improve Pulmonary Fibrosis 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
NOTES TO EDITORS
About the TOMORROW Trial
The phase II TOMORROW trial was a 12-month, randomized, double-blind, placebo-controlled trial conducted at 92 sites in 25 countries.1 The trial evaluated the safety and efficacy of oral BIBF 1120* at four dosage levels in 432 patients diagnosed with IPF, as defined by the American Thoracic Society (ATS) and European Respiratory Society (ERS).1,2
The primary endpoint for the TOMORROW trial was annual rate of decline in force vital capacity (FVC).1 Secondary endpoints included acute exacerbations, quality of life using the St. Georges Respiratory Questionnaire (SGRQ)and total lung capacity.1,6 In patients treated with 150 mg twice daily BIBF 1120*, FVC declined by 0.06 litres per year as compared with 0.19 litres per year in patients treated with placebo.1 This dose also resulted in a lower incidence of acute exacerbations versus placebo (2.4 versus 15.7 per 100 patient years; p=0.02).1 The decrease in quality of life measured by SGRQ was lower with BIBF 1120* than with placebo.
The most frequent adverse events were diarrhoea, nausea, and vomiting, which led to more discontinuations in the 150 mg bid group than in placebo (the respective rates were 11.8% vs. 0%, 4.7% vs. 0%, and 2.4% vs. 1.2%); liver transaminase increases were more frequent in the 150 mg twice daily group than placebo.1
The overall incidence of adverse events was comparable in all groups, as was the number of patients with serious or severe adverse events, and adverse events requiring hospitalisation.1 The proportion of patients with serious adverse events was numerically lower in the 150 mg twice daily dose group (27.1 percent) compared with placebo (30.6 percent).1
TOMORROW Data at ERS 2011 Annual Congress
The primary manuscript, the NEJM paper will be presented at the European Respiratory Society (ERS) 2011 Annual Congress on Monday 26 September 2011. Additional results of the TOMORROW trial will be presented during oral sessions at ERS on Sunday 25 September and at a BI-sponsored symposium on Monday 26 September.
About BIBF 1120
BIBF 1120* is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF).1 It targets three growth factors: the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR).1,8 These receptors have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis. By blocking these signaling pathways that are involved in fibrotic processes, it is believed that BIBF 1120* has the potential to reduce disease progression, namely slowing the decline of lung function.1,8 BIBF 1120* is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.1,8,9
About Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are only limited treatment options available to date.2 The incidence of IPF can vary considerably and estimate range from 14-43 per 100,000;10 additionally, there is some evidence that the patient population is increasing.2 Overall, some five million individuals worldwide may suffer from IPF.11 IPF is characterised by inflammation and scarring of lung tissue and loss of lung function over time.2,12,13 Development of scarred tissue is called fibrosis.13 Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen.13 As a result, individuals with IPF experience shortness of breath and often have difficulty participating in everyday physical activities.14
Boehringer Ingelheim: Leading respiratory forward
Treatment of COPD has been a major area of focus for Boehringer Ingelheim for decades and significant resources are dedicated to research in this field. More recently, the Company has also branched out into developing treatment options for other airway diseases, including asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory indications. Boehringer Ingelheim’s respiratory portfolio covers a wide range of treatment options and includes Spiriva® (tiotropium), Berodual® (fenoterol/ipratropium bromide), Berotec® (fenoterol), Combivent® (ipratropium bromide/salbutamol) and Atrovent® (ipratropium bromide).
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual co-operation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.
In 2010, Boehringer Ingelheim posted net sales of about €12.6 billion while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.
Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the USA.
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.