New Analyses Further Add to the Efficacy and Safety Profile of OFEV® (nintedanib) in Idiopathic Pulmonary Fibrosis (IPF)

  • First data from post-marketing surveillance was consistent with the safety profile of OFEV® from the clinical studies supporting its FDA approval1
  • In two separate post-hoc analyses of an open-label extension of the Phase III trials, in one analysis of OFEV® treated patients, a similar decline in lung function was observed regardless of the person’s level of disease severity at the start of the study while another study suggests that OFEV® was effective over approximately two years2,3
  • Post-hoc analysis of the Phase III trials suggests that OFEV® had a similar effect even if people reduced or held doses to manage side effects4

Ingelheim, Germany, 13 November 2015 – Boehringer Ingelheim today announced the presentation of new analyses of OFEV® for the treatment of idiopathic pulmonary fibrosis (IPF) at the Pulmonary Fibrosis Foundation’s PFF Summit 2015 in Washington, D.C. In 2014, OFEV® became one of the first FDA-approved drug treatments for IPF, a rare and serious lung disease that causes permanent scarring of the lungs.

In a post-marketing surveillance study in the United States, treatment with OFEV® in the real-world clinical setting showed a safety profile consistent with that observed in clinical trials supporting its approval by the FDA.1

 

Imre Noth“The approval of OFEV® was supported by evidence from three well-designed studies part of a comprehensive clinical trial programme and it is key to continually analyse the real-world experiences of people on therapy given the limited data on IPF,” said Imre Noth, M.D., Professor of Medicine and Director of the Interstitial Lung Disease Programme at The University of Chicago, and lead author of the analysis. “These first results from the post-marketing surveillance study, which showed a consistent safety profile of OFEV® as described in the prescribing information, are important because they provide healthcare providers with additional information when considering OFEV® for their patients with IPF.”

First data from U.S. surveillance study
Post-marketing surveillance of the safety and tolerability of OFEV® in the United States has been collected in the Boehringer Ingelheim drug safety and reporting database since OFEV® was first approved on October 15, 2014. Until May 31, 2015, 3,838 people were treated with OFEV® for a length of time ranging from 14 to 265 days (on average 88 days).1
The most frequently reported side effects were gastrointestinal in nature and included diarrhea, nausea, vomiting and decreased appetite. Diarrhea was the most frequently reported individual side effect, occurring at a similar frequency to that observed in the clinical trials supporting approval.1 No new safety concerns were identified.1

Researchers also presented two post-hoc analyses from an open-label, extension of the one-year Phase III INPULSIS®studies, known as INPULSIS®ON. People with IPF who completed the 52-week treatment period and a four-week follow-up period in the identically-designed INPULSIS® trials were invited to receive open-label treatment with OFEV® to assess its long-term safety and tolerability. INPULSIS®-ON included 734 participants (more than 90 percent of those completing the INPULSIS® trials), including 304 people who initiated OFEV® after receiving placebo in the Phase III trials and 430 people who were on OFEV® in the INPULSIS® trials and continued to receive treatment.

New results in people with IPF with severe lung impairment (NCT01619085)
The first analysis evaluated treatment effect in people with IPF who had severe lung impairment (less than 50 percent forced vital capacity [FVC] predicted). The Phase III INPULSIS® studies excluded people with severe lung impairment; however, they were allowed to enter the extension study even if their lung function declined to severe levels during the initial one-year treatment period.3 The new analysis reports that, in patients treated with OFEV®, a similar decline in lung function was observed in people with severe lung impairment when compared to people with mild to moderate impairment (greater than or equal to 50 percent predicted).2​

Danny McBryanNew long-term efficacy data in people with IPF (NCT01619085)
The second analysis suggests OFEV® had a long-term effect on slowing FVC decline, a measure of disease progression, for approximately two years, or 100 weeks.3

Overall, the most common adverse events were diarrhea, nausea, cough, common cold (nasopharyngitis), bronchitis, difficult or labored breathing (dyspnea), IPF disease progression, decreased appetite, weight decreased and vomiting. The most frequent serious adverse event reported was IPF, which includes disease worsening and acute exacerbations.2​

“At Boehringer Ingelheim, we are committed to improving the understanding of IPF and the role that OFEV® plays in the treatment of this disease,” said Danny McBryan, M.D., vice president, Clinical Development and Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “Collectively, these analyses support the suggestion that OFEV® continues to be effective out to approximately two years and that the decline in lung function is similar in people receiving OFEV® with severe or mild to moderate impairment of lung function. These results add to our understanding of OFEV® by providing insight into the impact over a longer period of time and in patients that were not included in the studies supporting its approval.”

Effect of dose reductions, treatment interruptions and dose intensity on the effect of OFEV® (NCT01335464 and NCT01335477)
A fourth abstract was a post-hoc analysis of combined data from the Phase III INPULSIS® trials among people who had to reduce OFEV® dosing from 150 mg twice daily to 100 mg twice daily or interrupt treatment to manage side effects, and patients who did not have their dose modified.

The analysis showed that dose reductions or interruptions did not affect the efficacy of treatment in people with IPF.4 Specifically, OFEV® had a similar effect on FVC decline (a measure of disease progression) irrespective of having greater than or equal to one dose reduction/interruption and less than or equal to 90 percent dose intensity. Overall, the average changes in lung function (as measured by a change in FVC from baseline to 52 weeks) were similar whether or not people had at least one dose reduction/interruption (-87.5 mL and -89.6 mL, respectively), or a reduction in dose intensity (-72.0 mL for less than or equal to 90 percent and -94.2 mL for greater than 90 percent).4

Additional information

About OFEV® (nintedanib)
OFEV® is a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim for IPF.5 OFEV®, one capsule twice a day, slows disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types.6,7,8,9,10,11 This includes patients with early disease (FVC >90% pred)8 limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT)9 and those with emphysema.10 Side effects with OFEV® can be effectively managed in most patients.6

OFEV® targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly OFEV® inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).6,12,13 It is believed that OFEV® reduces disease progression in IPF and slows the decline in lung function by blocking the signalling pathways that are involved in fibrotic processes.6,14​

About idiopathic pulmonary fibrosis
IPF is a progressive and life threatening lung disease.15 IPF affects as many as 14–43 people per 100,000 worldwide.16,17 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.13,18 Development of scarred tissue is called fibrosis. 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.19 As a result, individuals with IPF experience shortness of breath, a non-productive cough and often have difficulty participating in everyday physical activities.19 Acute IPF exacerbations are defined as rapid deteriorations of symptoms within days or weeks. These events can occur at any point in the course of the disease, even at first presentation.20 All patients with IPF are at risk of acute IPF exacerbations.21

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 146 affiliates and a total of more than 47,700 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.

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 2014, Boehringer Ingelheim achieved net sales of about 13.3 billion euros. R&D expenditure corresponds to 19.9 per cent of its net sales.

Intended audiences:
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

Referências

  1. Noth I, et al. Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis (IPF): data from post-marketing surveillance in the United States. Abstract presented at the PFF Summit 2015. Washington, D.C. November 12-14, 2015.
  2. Wuyts WA, et al. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis (IPF) and forced vital capacity (FVC) ≤50% predicted. Abstract presented at the PFF Summit 2015. Washington, D.C. November 12-14, 2015.
  3. Kaye M, et al. Long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis (IPF). Abstract presented at the PFF Summit 2015. Washington, D.C. November 12-14, 2015.
  4. Richeldi L, et al. Effect of dose reductions, treatment interruptions and dose intensity on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF): results from the INPULSIS® trials. Abstract presented at the PFF Summit 2015. Washington, D.C. November 12-14, 2015.
  5. Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079-1087.
  6. Richeldi L, du Bois RM, Raghu G, et al; for the INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;380(22):2071-2082
  7. OFEV® Summary of Product Characteristics. Boehringer Ingelheim International GmbH. January 2015.
  8. Kolb M, Richeldi L, Kimura T, Stowasser S, Hallmann C, du Bois RM. Effect of baseline FVC on decline in lung function with nintedanib in patients with IPF: results from the INPULSIS® trials. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
  9. Raghu G, Wells A, Nicholson AG, et al. Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS® trials in IPF. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
  10. Cottin V, Taniguchi H, Richeldi L, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS® trials. Abstract presented at the 18th International Colloquium on Lung and Airway Fibrosis; Mont Tremblant, Canada, September 20-24, 2014. Available at: http://iclaf.com/conference/index.php/2014/ICLAF/paper/view/151. Accessed November 11, 2015.
  11. Costabel U., et al. Efficacy of nintedanib in idiopathic pulmonary fibrosis across pre-specified subgroups in INPULSIS®. AJRCCM. 2015; 15-10031.
  12. Selman M, et al. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001;134:136-51.
  13. Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
  14. Wollin L, et al. Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase Inhibitor Nintedanib in Experimental Models of Lung Fibrosis. J Pharmacol Exp Ther. 2014;349:209–220.
  15. Ley B., et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. AJRCCM. 2011;183:431–40.
  16. Raghu G, et al. Incidence and prevalence of idiopathic pulmonary fibrosis.
  17. Am J Respir Crit Care Med. 2006;174:810-816.
  18. Fernández Pérez E, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137:129-37.
  19. NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/. Accessed November 11, 2015.
  20. Pulmonary Fibrosis Foundation. Symptoms. Available at: http://www.pulmonaryfibrosis.org/life-with-pf/about-pf. Accessed November 11, 2015.
  21. Collard H, et al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2007;176:636–643.