New data demonstrate sustained long-term efficacy of OFEV^®* on slowing disease progression and safety in patients with IPF

Ingelheim/Amsterdam, 29 September 2015 – An interim analysis of the INPULSIS^®-ON extension trial has confirmed the efficacy and safety of OFEV^®* (nintedanib) previously observed in the INPULSIS^® trials.1 The results were presented at the European Respiratory Society (ERS) International Congress 2015, and confirm that OFEV^®* has a long-term effect on slowing disease progression and a manageable side effect profile in patients with idiopathic pulmonary fibrosis (IPF).1 This new data is important in light of the fact that IPF is a life-threatening and progressive disease, requiring patients to be on long-term treatment.4

The INPULSIS^®-ON interim analysis showed that the change from baseline in forced vital capacity (FVC) at 48 weeks in patients continuing treatment with OFEV^®* in the extension trial1 was comparable to what was observed in the 52 weeks INPULSIS^® trial.1 This provides further evidence that the beneficial effect of OFEV^®* on slowing disease progression is maintained in the long-term.1

“The safety and efficacy data presented for OFEV^®* is very reassuring with regards to the long-term outcomes of treatment with OFEV^®* and its effect on slowing disease progression,” said Professor Luca Richeldi, Professor of Respiratory Medicine at the University of Southampton, United Kingdom. “They add further weight to the growing body of evidence in support of OFEV^®* as an effective and manageable treatment for IPF. When managing IPF it is important that physicians discuss with their patients what to expect from treatment and which treatment is right for them, to initiate this treatment early and then to ensure the patient stays on it as long as possible.”

Key results from the interim analysis of INPULSIS^®-ON
INPULSIS^®-ON is an open-label single arm study. More than 90% of IPF patients participating in INPULSIS^® and eligible for open-label treatment with nintedanib in INPULSIS^®-ON opted to participate. Patients on placebo treatment in the INPULSIS^® trials newly initiated treatment with OFEV^®* in the extension trial and patients already treated with OFEV^®* in the INPULSIS trials continued to receive OFEV^®*. The effect of OFEV^®* on the mean change from baseline in FVC at week 48 of the INPULSIS^®-ON trial was comparable to the one seen at 52 weeks in the INPULSIS^® trial:

• In INPULSIS^®-ON: -87 mL for all patients, -96,4 mL for patients continuing treatment with OFEV^® in the extension trial and -73,1 mL for patients initiating treatment with OFEV^®1
• In INPULSIS^® (pooled data): -88,9 mL (OFEV^®) vs. -203,0 mL (placebo)1

The analysis substantiates the effects of OFEV^®* on slowing disease progression and confirms the long-term efficacy of OFEV^®*.1 Additionally no new safety signals were identified following long-term treatment with OFEV^®* in INPULSIS^®-ON.1 The most frequent adverse events were gastrointestinal in nature with diarrhoea affecting 64% of patients but leading to drug discontinuation in only 5%.1

Effect of OFEV^®* on a broad range of IPF patients**
New subgroup-analyses from the INPULSIS^® study presented at the congress examined whether OFEV^®*had a consistent effect on patients with IPF who were also taking commonly used medications, including anti-acids and corticosteroids, when they were enrolled in the study.2,3

Anti-acid medications are often given to patients with IPF to manage gastroesophageal reflux disease (GERD), which is common in patients with IPF and is considered to be a risk factor for IPF disease progression and acute exacerbations.5 IPF patients are also sometimes treated with low doses of corticosteroids (e.g. prednisone) and therefore subjects receiving low doses of corticosteroids were allowed in the INPULSIS^® trials.6

The analyses confirm that these concomitant medications taken at baseline do not influence the beneficial effect of OFEV^®* on annual rate of FVC decline.2,3

The two analyses provided further evidence that OFEV^®* slows disease progression in a broad range of IPF patients**.2,3

These data are presented at the European Respiratory Society International Congress on 29 September 2015 at 14.45 CEST in Room 4.1. The corresponding abstracts can be found within the online programme, here: http://www.erscongress.org/programme-2015/access-the-programme.html

• Interim analysis of nintedanib in an open-label extension of the INPULSIS^® trials (INPULSIS^®-ON)
• Effect of anti-acid medication on reduction in FVC decline with nintedanib
• Effect of baseline corticosteroid medication on reduction in FVC decline with nintedanib

New IPF treatment guidelines emphasise the role of OFEV^®* in the treatment of IPF
In July 2015, the international evidence-based 2015 ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis was published giving a conditional recommendation for the use of OFEV^® (nintedanib*) in patients with IPF***.7 The committee noted the high value of OFEV^® on patient-important outcomes such as disease progression as measured by rate of forced vital capacity (FVC) decline and mortality. The recommendation also takes into account the expected cost of treatment and potentially significant adverse effects.

Notes to Editor

About the INPULSIS^® Phase III trials with OFEV^® (nintedanib*)
The double blind, randomised, placebo-controlled trials involving 1,066 patients across 24 countries 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.6 The trials had an identical design, matched dosing, inclusion criteria and endpoints.6,8 The primary endpoint was the annual rate of decline in FVC. Key secondary endpoints were: change from baseline in health-related quality of life, as assessed by the Saint George’s Respiratory Questionnaire (SGRQ) and time to first acute IPF exacerbation.

Key results showed: 6   

• Nintedanib* slowed disease progression in IPF by reducing the annual decline in lung function by 50% compared to patients taking placebo
• Nintedanib* significantly reduced the risk of adjudicated acute exacerbations‡ by 68% in the pooled data set. This can be crucial given that approximately 50% of patients hospitalised for an acute IPF exacerbation die during hospitalisation.9
• There was a significant benefit of nintedanib* versus placebo in change in SGRQ total score in INPULSIS^®-2, but no significant difference between groups in INPULSIS^®-1

In both INPULSIS^® trials, the most common adverse events were gastrointestinal in nature, of mild or moderate intensity, generally manageable and rarely leading to treatment discontinuation.6 The proportion of patients with serious adverse events was similar in all groups.6 The most frequent adverse event in the nintedanib* groups was diarrhoea, 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.6

About the INPULSIS^®-ON open label extension trial
Patients who completed the 52-week treatment period and a 4-week follow-up period in the INPULSIS^®trials were invited to receive open-label treatment with nintedanib* as part of an extension trial to assess the long-term safety and tolerability of nintedanib*. The INPULSIS^®-ON (Clinicaltrial.gov trial identifier: NCT01619085) trial included 734 patients and is currently ongoing.

About OFEV^® (nintedanib*)
Nintedanib* is a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim for IPF.10OFEV^®, 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.6,11,12,13,14,15,16 This includes patients with early disease (FVC >90% pred),12 limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT)13 and those with emphysema.14 Side effects with nintedanib* can be effectively managed in most patients.6

Nintedanib* targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly nintedanib* inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).4,6,17 It is believed that nintedanib* reduces disease progression in IPF and slows the decline in lung function by blocking the signalling pathways that are involved in fibrotic processes.6,17,18

About OFEV^® (nintedanib*) approvals (up to 31st August 2015)

• The FDA approved OFEV^®* for the treatment of IPF on 15 October 2014
  The European Commission approved OFEV^®* for the treatment of IPF on 15 January 2015
• Health Canada approved OFEV^®* for the treatment of IPF on 25 June 2015
  The Ministry of Health, Labour and Welfare in Japan approved OFEV^®* for the treatment of IPF on 3 July 2015
• Swissmedic in Switzerland approved OFEV^®* for the treatment of IPF and to slow disease progression on 13 August 2015

About idiopathic pulmonary fibrosis
IPF is a progressive and life threatening lung disease.19 IPF affects as many as 14–43 people per 100,000 worldwide.20,21 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.4,22 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.22 As a result, individuals with IPF experience shortness of breath, a non-productive cough and often have difficulty participating in everyday physical activities.23 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.24 All patients with IPF are at risk of acute IPF exacerbations.24

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