Nintedanib receives positive CHMP opinion in EU for the treatment of Idiopathic Pulmonary Fibrosis

Boehringer Ingelheim announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for nintedanib* (suggested brand name OFEV®) for the treatment of patients with idiopathic pulmonary fibrosis (IPF).

Boehringer Ingelheim announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for nintedanib* (suggested brand name OFEV®) for the treatment of patients with idiopathic pulmonary fibrosis (IPF).

• Data showed that nintedanib slowed disease progression by reducing annual decline in lung function by approximately 50% (1)
• Nintedanib* also significantly reduced the risk of adjudicated acute exacerbations by 68% (p=0.001) (2)

Results from the Phase III INPULSIS® trials, published in the New England Journal of Medicine in May 2014, showed that nintedanib* significantly slowed disease progression in patients with IPF. (1) The opinion follows the recent Food and Drug Administration (FDA) approval of nintedanib* for the treatment of IPF.

“This decision is very encouraging as patients with IPF currently have very limited treatment options,” said INPULSIS® study investigator Professor Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease at the University of Southampton, United Kingdom. “For the first time we have a drug that has consistently met the primary endpoint in two large Phase III trials, confirming the results of the Phase II trial.”

Idiopathic pulmonary fibrosis (IPF) is a progressive and severely debilitating lung disease with a high mortality rate. (3) It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing. (4) In patients with IPF, lung function loss is measured by a decline in a patient’s forced vital capacity (FVC), the maximum volume of breath that can be exhaled. The average IPF patient has lung volume loss of between 150–200ml per year, compared to a normal adult lung volume decline of approximately 50ml per year. (5,6)

Dr Charles de Wet, UK Medical Director at Boehringer Ingelheim, commented, “Boehringer Ingelheim welcomes the decision by the CHMP to grant nintedanib a positive opinion. IPF is a highly debilitating disease for patients and there are currently only limited treatment options that are able to slow disease progression. We hope that we are able to make nintedanib available to these patients in the EU soon.”

The CHMP’s positive opinion is based on pivotal data from the replicate Phase III INPULSIS® trials involving 1066 patients from 24 countries. (1)

INPULSIS® results showed that nintedanib* slowed disease progression by reducing the annual rate of decline in lung function by approximately 50% in IPF patients. This included patients with early disease (forced vital capacity (FVC) >90% predicted), limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT) and those with emphysema. (1) Nintedanib* also significantly reduced the risk of adjudicated acute exacerbations by 68%. (1,2) This is important given that approximately half of patients hospitalised for an acute IPF exacerbation die during hospitalisation. (7)

The most frequent adverse event in the nintedanib* groups was diarrhoea, reported in 62% of patients vs. 19% in the placebo arm (INPULSIS®-1) and 63% versus 18% (INPULSIS®-2). Less than 5% of those who experienced diarrhoea in the nintedanib* groups of INPULSIS®-1 and INPULSIS®-2 discontinued treatment due to this event. (1)

Nintedanib* in IPF has been granted accelerated assessment by the EMA. It is the first targeted treatment for IPF that has consistently demonstrated the ability to slow disease progression by significantly reducing decline in lung function (p<0.001) with a manageable side effect profile. (1)

References:

1. Richeldi L, Du Bois R, Raghu G et al. Efficacy and Safety of nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med 2014; published online 18 May:DOI: 10.1056/NEJMoa1402584.
2. Richeldi L, Du Bois R, Raghu G et al. Efficacy and Safety of nintedanib in Idiopathic Pulmonary Fibrosis – Supplementary Appendix. N Engl J Med 2014; published online 18 May:DOI: 10.1056/NEJMoa1402584.
3. Raghu G, Collard H, Egan J. 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.
4. Collard H, Moore B, Flaherty K et al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2007;636-643.
5. Ley B, Collard H, King T. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2011; 183:431-440.
6. Association for Respiratory Technology and Physiology. Predicted FVC for Men (18 to 60). 2014. Available at: http://www.alpha1awareness.org.uk/wp-content/uploads/2012/06/Predicted-FEV1-FVD-Men.pdf. Last accessed: November 2014.
7. Song J, Hong-SB, Koh Y et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J 2011; 34:356-363.