1. Long-term Data: INPULSIS®-ON
Filming: 15th of Febuary 2016, London, UK
Prof. Vincent Cottin
Prof. Luca Richeldi

2. INPULSIS® and INPULSIS®-ON: Study design1,2
Patients who completed the 52-week treatment period and follow-up visit 4 weeks later in an INPULSIS® trial were eligible to enter INPULSIS®-ON.
Dose reduction to 100 mg bid and treatment interruption were allowed to manage adverse events; dose re-escalation to 150 mg bid was permitted.
INPULSIS®
INPULSIS®-ON
Patients randomized 3:2
To receive either nintedanib or placebo
Double-blind, placebo-controlled
Open-label extension trial
Nintedanib 150 mg bid (n= 638)
Continuing nintedanib (n=430) R
Placebo (n=423)
Initiating nintedanib (n=304)
52 Weeks
(trial period)
No treatment*
*Per protocol, the off-treatment period between INPULSIS® and INPULSIS®-ON could be between 4 and 12 weeks.
1. Crestani B, et al. Abstract presented at ERS Richeldi L, et al. NEJM 2014;370:2071–2082.
references

3. Exposure times in INPULSIS® and INPULSIS®-ON
Mean (SD; min–max) total duration of exposure for patients treated with nintedanib in both INPULSIS® and INPULSIS®-ON was 29.2 (6.6; 11.9–40.6) months.1 Exposure times (Interim analysis: November 2014)1
INPULSIS®
INPULSIS®-ON
Nintedanib (n=638)
Placebo (n=423)
Continuing nintedanib (n=430)
Initiating nintedanib (n=304)
Exposure, months
Mean (SD)
10.3 (3.4)
10.8 (2.8)
17.2 (6.6)
16.0 (7.3)
Minimum, maximum
0.0, 12.7
0.0, 13.1
0.1, 28.8
0.0, 28.8
1. Crestani B, et al. Abstract presented at ERS 2015.
references

4. Pooled INPULSIS® analysis at 52 weeks1
An interim analysis of the INPULSIS®-ON trial confirmed the long-term efficacy of nintedanib in patients with IPF1,2
Change from baseline in FVC at week 52 in INPULSIS® and at week 48 in INPULSIS®-ON1,2
Pooled INPULSIS® analysis at 52 weeks1
INPULSIS®-ON at 48 weeks2
Nintedanib (n=519)
Placebo (n=345)
Continuing nintedanib (n=352)
Initiating nintedanib (n=233)
Mean (SEM) observed change from baseline in FVC (mL)
1. Richeldi L, et al. NEJM 2014;370:2071– Crestani B, et al. Abstract presented at ERS 2015.
references

5. Safety and tolerability profile of nintedanib confirmed beyond 2 years1,2
Adverse Events (Interim analysis: November 2014)1
N (%)
INPULSIS®
INPULSIS®-ON
Nintedanib (n=638)
Placebo (n=423)
Continuing nintedanib (n=430)
Initiating nintedanib (n=304)
Exposure, months, mean (SD)
10.3 (3.4)
10.8 (2.8)
17.2 (6.6)
16.0 (7.3)
Adverse events
609 (95.5)
379 (89.6)
399 (92.8)
294 (96.7)
Severe adverse events
174 (27.3)
99 (23.4)
130 (30.2)
104 (34.2)
Adverse events leading to drug discontinuation
123 (19.3)
55 (13.0)
86 (20.0)
87 (28.6)
Serious adverse events
194 (30.4)
127 (30.0)
180 (41.9)
120 (39.5)
Fatal adverse events
37 (5.8)
31 (7.3)
45 (10.5)
30 (9.9)
There were no new safety concerns identified after 2 years.1,2
*A severe adverse event was related to intensity and was defined as an event that was incapacitating or that caused an inability to work or to perform usual activities. **A serious adverse event was defined as any adverse event that resulted in death, was immediately life-threatening, resulted in persistent or clinically significant disability or incapacity, required or prolonged hospitalization, was related to a congenital anomaly or birth defect, or was deemed serious for any other reason.
1. Crestani B, et al. Abstract presented at ERS Crestani B, et al. AJRCCM 191;2015:A1020.

6. Safety and tolerability profile of nintedanib confirmed beyond 2 years1,2
Special Adverse Events: Cardiac and Bleeding Adverse Events (Interim analysis: November 2014)1
N (%)
INPULSIS®
INPULSIS®-ON
Nintedanib (n=638)
Placebo (n=423)
Continuing nintedanib (n=430)
Initiating nintedanib (n=304)
Exposure, months, mean (SD)
10.3 (3.4)
10.8 (2.8)
17.2 (6.6)
16.0 (7.3)
Cardiac disorders*
64 (10.0)
45 (10.6)
57 (13.3)
32 (10.5)
Serious cardiac disorders*
32 (5.0)
23 (5.4)
23 (5.3)
15 (4.9)
Ischaemic heart disease†
27 (4.2)
17 (4.0)
20 (4.7)
9 (3.0)
Myocardial infarction
7 (1.1)
2 (0.5)
3 (0.7)
0 (0.0)
Acute myocardial infarction
3 (0.5)
1 (0.2)
Bleeding‡
66 (10.3)
33 (7.8)
45 (10.5)
28 (9.2)
Serious bleeding‡
8 (1.3)
6 (1.4)
4 (0.9)
*System organ class. †Based on broad scope definition of SMQs. ‡Bleeding is based on standardised MedDRA query “haemorrhage terms (excluding laboratory terms)”.
1. Crestani B, et al. Abstract presented at ERS 2015.
references

7. Conclusions
An interim analysis of the INPULSIS®-ON trial confirmed the long-term efficacy and safety profile of nintedanib in patients with IPF:
The decline in FVC in patients continuing or initiating nintedanib in INPULSIS®- ON was similar to the decline in FVC with nintedanib in INPULSIS®.
This suggests that the treatment effect of nintedanib on slowing disease progression persists for 2 years.
Long-term nintedanib treatment (up to 40 months) had a manageable safety and tolerability profile, with no new safety signals identified.
1. Crestani B, et al. Abstract presented at ERS 2015.