IPF Phase III results published in NEJM show nintedanib* slows disease progression

Ingelheim, Germany, 18 May 2014 – Results from the Phase III INPULSIS^™ trials, published online today in the New England Journal of Medicine, show nintedanib* significantly slowed disease progression in patients with idiopathic pulmonary fibrosis (IPF).¹ Nintedanib* is the first targeted treatment for IPF to consistently meet the primary endpoint in two international Phase III trials with identical design.

IPF is a debilitating and fatal lung disease, with a median survival of 2–3 years after diagnosis.² It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing.³ The average IPF patient has a lung function loss, measured by forced vital capacity (FVC), of 150–200mL per year.⁴

In the two 52 week INPULSIS^™ trials, involving 1,066 patients, nintedanib* significantly reduced the annual decline in FVC by approximately 50% compared to patients taking placebo. The annual rate of FVC decline in the two trials was:¹
 

• ­INPULSIS^™-1: -114.7mL (nintedanib*) vs. -239.9mL (placebo)
• INPULSIS^™-2: -113.6mL (nintedanib*) vs. -207.3mL (placebo)

"Patients with IPF currently have very limited treatment options and there is a high unmet need for effective treatments that can specifically alter the course of this deadly disease by slowing disease progression," said study investigator Professor Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease at the University of Southampton, United Kingdom. "These results should be very welcomed, because for the first time we have a drug that has consistently met the primary endpoint in two large Phase III trials, after the supportive results of the Phase II trial."

Both key secondary endpoints were met in the INPULSIS^™-2 trial. There was significantly less deterioration in quality of life (measured by the St. George’s Respiratory Questionnaire) and a reduced risk of a first acute exacerbation in patients taking nintedanib* versus placebo.¹

"The result on acute exacerbations is of particular clinical importance," Professor Richeldi said. "Acute exacerbations are rapid and unexplained episodes of deterioration in IPF leading to death in approximately half of the patients."

In INPULSIS^™-1, there was no statistically significant difference between the nintedanib and placebo groups in the key secondary endpoints.¹

In both trials, the most common adverse events were gastrointestinal in nature, of mild to moderate intensity, generally manageable, rarely leading to treatment discontinuation.¹

The most frequent adverse event in the nintedanib groups was diarrhoea, which was reported in 62% vs. 19% (INPULSIS^™-1) and 63% vs. 18% (INPULSIS^™-2) of patients in the nintedanib* vs. placebo groups, respectively). Less than 5% of patients in the nintedanib* groups of INPULSIS^™-1 and INPULSIS^™-2 discontinued treatment due to this event.¹

The proportion of patients with serious adverse events was similar in all groups.

NOTES TO EDITOR

About the INPULSIS^™ trials
The double blind, randomised and placebo-controlled trials evaluated the effect of oral nintedanib*, 150 mg twice daily, on the annual rate of decline in forced vital capacity (FVC), in patients with IPF over 52 weeks. The trials had an identical design, matched dosing, inclusion criteria, and endpoints.^5,6

The primary endpoint was the annual rate of decline in FVC (expressed in mL over 52 weeks). Key secondary endpoints were: change from baseline in health-related quality of life, as assessed by the Saint-George’s Respiratory Questionnaire (SGRQ); time to first acute exacerbation (number of days). Other secondary endpoints included change from baseline in FVC, overall survival, respiratory mortality, on-treatment survival.^5,6

Patients included in the trials were at least 40 years of age, diagnosed with IPF within five years prior to enrolment, based on the most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) IPF guidelines for diagnosis and management.^5,6

Eligibility into the studies was assessed by central review of the high resolution computerised tomography pattern by an expert radiologist and surgical lung biopsy, if available, by an expert pathologist.^5,6

More information can be found on clinicaltrials.gov (identifiers NCT01335464 and NCT01335477).

About nintedanib
Nintedanib* is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF).⁷ It targets growth factor receptors, which have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis, most importantly the platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).^7,8,9 By blocking the signalling pathways that are involved in fibrotic processes, it is believed that nintedanib* has the potential to reduce disease progression in IPF by slowing the decline of lung function.^7,8,10 Nintedanib* is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.

About idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are limited treatment options.² IPF affects as many as 14–43 people per 100,000 worldwide.^11,12 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.^8,13 Development of scarred tissue is called fibrosis.² 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.³ As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.¹⁴

For more information please visit www.inIPF.com

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative “Making more Health” and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about €14.1 billion. R&D expenditure corresponds to 19.5% of its net sales.