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    • OFEV was studied across 3 rigorously controlled trials with a total of 1231 patients with IPF1

    INPULSIS®-1, INPULSIS®-2, AND TOMORROW WERE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 52-WEEK TRIALS1-3

    INPULSIS®-1 and INPULSIS®-21

    INPULSIS-1 and INPULSIS-2
    INPULSIS-1 and INPULSIS-2

    Primary endpoint1

    • Annual rate of decline in FVC over 52 weeks (measured in mL/year)

    The clinical trials recruited a range of patients with IPF with FVC ≥50% predicted1-3

    Key inclusion criteria for INPULSIS®-1 and -2 and TOMORROW

    • Age ≥40 years (no upper limit)
    • Diagnosis of IPF within 5 years
    • Chest HRCT performed within 12 months
    • HRCT pattern and, if available, surgical lung biopsy pattern consistent with diagnosis of IPF
    • FVC ≥50% of predicted value (no upper limit)
    • DLCO 30%–79% of predicted value

    Exclusion criteria1

    • Relevant airway obstruction (ie, prebronchodilator FEV1/FVC <0.7)
    • Likely to receive a lung transplant during the study (in the opinion of the investigator)
    • Had >1.5 times ULN of ALT, AST, or bilirubin
    • Known risk or predisposition to bleeding
    • Receiving a full dose of anticoagulation medication
    • Recent history of myocardial infarction or stroke
    • Received other investigational therapy, azathioprine, cyclophosphamide, or cyclosporine A within 8 weeks of entry into this trial
    • Received N-acetylcysteine and prednisone (>15 mg/day or equivalent) within 2 weeks

    IF SURGICAL LUNG BIOPSY WAS NOT AVAILABLE, PATIENTS NEEDED TO HAVE ONE OF THE FOLLOWING COMBINATIONS OF RADIOLOGICAL CRITERIA TO BE ELIGIBLE: A+B+C, A+C,* OR B+C2,3

    Ico PlaceholderA
    Definite honeycomb lung destruction with basal and peripheral predominance
    Ico Placeholder B
    Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis with basal and peripheral predominance
    Ico Placeholder (2)
    The absence of atypical features, specifically nodules and consolidation. Ground-glass opacity, if present, should be less extensive than reticular opacity pattern

     *  Only permitted in the INPULSIS® trials.2,3

    The patient population was similar across clinical trials1-4

    Key demographic and baseline characteristics

    INPULSIS®-1

    Demographics

     OFEV (n=309)Placebo (n=204)
    Mean age, years (SD)66.9 (8.4)66.9 (8.2)
    Male sex, %81.279.9
    White, %64.166.2
    Asian, %21.420.1
    Ex- or current smoker, %77.075.0

    Lung function

     OFEV (n=309)Placebo (n=204)
    Mean FVC, mL (SD)2757 (735)2845 (820)
    Mean FVC, % predicted (SD)79.5 (17.0)80.5 (17.3)
    FEV1: FVC, % (SD)81.5 (5.4)80.8 (6.1)
    DLCO, % predicted (SD)47.8 (12.3)47.5 (11.7)

    Diagnostic criteria

     OFEV (n=309)Placebo (n=204)

    HRCT, % (n), Evidence of

     honeycombing

    		49.1 (152)52.9 (108)

    HRCT, % (n), No evidence of 

    honeycombing

    		48.2 (149)44.1 (90)
    Emphysema on HRCT, %38.238.2
    Lung biopsy, % (n)19.4 (60)16.2 (33)

    INPULSIS®-2

    Demographics

     OFEV (n=329)Placebo (n=219)
    Mean age, years (SD)66.4 (7.9)67.1 (7.5)
    Male sex, %77.878.1
    White, %49.251.6
    Asian, %38.939.7
    Ex- or current smoker, %68.767.6

    Lung function

     OFEV (n=329)Placebo (n=219)
    Mean FVC, mL (SD)2673 (776)2619 (787)
    Mean FVC, % predicted (SD)80.0 (18.1)78.1 (19.0)
    FEV1: FVC, % (SD)81.8 (6.3)82.4 (5.7)
    DLCO, % predicted (SD)47.0 (14.5)46.4 (14.8) 

    Diagnostic criteria

     OFEV (n=329)Placebo (n=219)

    HRCT, % (n), Evidence of 

    honeycombing

    		52.9 (174)60.8 (133)

    HRCT, % (n), No evidence of 

    honeycombing

    		44.7 (147)37.4 (82)
    Emphysema on HRCT, %41.340.2
    Lung biopsy, % (n)25.5 (84)23.7 (52)

    TOMORROW

    Demographics

     OFEV (n=85)Placebo (n=85)
    Mean age, years (SD)65.4 (7.8)64.8 (8.6)
    Male sex, %76.574.1
    White, %71.876.5
    Asian, %28.223.5
    Ex- or current smoker, %70.667.1

    Lung function

     
     

    OFEV (n=85)

    		Placebo (n=85)
     

    Mean FVC, mL (SD)

     

    2700 (800)

     

    2800 (800)

     

    Mean FVC, % predicted (SD)

     

    79.1 (18.5)

     

    81.7 (17.6)

     

    FEV1: FVC, % (SD)

     

    81.0 (7.3)

     

    81.8 (5.6)

     

    DLCO, % predicted (SD)

     

    47.5 (11.0)

     

    48.4 (12.9) 

    Diagnostic criteria

     OFEV (n=85)Placebo (n=85)

    HRCT, % (n), Evidence of 

    honeycombing

    		38.8 (33)28.2 (24)

    HRCT, % (n), No evidence of 

    honeycombing

    		61.2 (52)67.1 (57)
    Emphysema on HRCT, %27.122.4
    Lung biopsy, % (n)34.1 (29)22.4 (19)

    OFEV is a disease-modifying agent proven to slow IPF progression by reducing lung function decline1,2,5-7

    OFEV (nintedanib) DEMONSTRATED REPRODUCIBLE REDUCTIONS IN THE ANNUAL RATE OF FVC DECLINE ACROSS 3 CLINICAL TRIALS1-3†

    inpulsis
    inpulsis

    † The annual rate of decline in FVC (mL/year) was analyzed using a random coefficient regression model.1

    The safety and tolerability profile of OFEV has been demonstrated in 3 clinical trials with over 1000 patients with IPF1

    THE MOST COMMON ADVERSE REACTIONS WERE GASTROINTESTINAL IN NATURE AND GENERALLY OF MILD OR MODERATE INTENSITY1

    Adverse reactions reported in ≥5% of OFEV (nintedanib)-treated patients and more commonly than placebo

     OFEV (n=723)Placebo (n=508)
    Diarrhea62%18%
    Nausea24%7%
    Abdominal pain‡15%6%
    Vomiting12%3%
    Liver enzyme elevation§14%3%
    Decreased appetite11%5%
    Headache8%5%
    Weight decreased10%3%
    Hypertension5%4%
    • The incidence of infections and infestations was similar in the OFEV and placebo groups across trials (TOMORROW, INPULSIS®-1, and INPULSIS®-2: 56% vs 55%, respectively; INBUILD®: 53% vs 56%, respectively; and SENSCIS®: 63% vs 64%, respectively)4
    • In addition, hypothyroidism was reported in patients treated with OFEV more than placebo (1.1% vs 0.6%). Alopecia was also reported in more patients treated with OFEV than placebo (0.8% vs 0.4%)1

    ‡ Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, and abdominal tenderness.1

    § Includes gamma-glutamyl transferase increased, hepatic enzyme increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic function abnormal, liver function test abnormal, transaminase increased, blood alkaline phosphatase increased, alanine aminotransferase abnormal, aspartate aminotransferase abnormal, and gamma-glutamyl transferase abnormal.1

    Dose reduction, treatment interruption, and discontinuation were used to manage adverse reactions1

     

    SYMPTOMATIC TREATMENT, DOSE REDUCTION, TREATMENT INTERRUPTION, AND/OR DISCONTINUATION WERE USED TO MANAGE DIARRHEA IN THE INPULSIS® TRIALS1,2

    intensity
    95% of diarrhea events were mild or moderate in intensity
    months
    The majority of diarrhea events occurred within the first 3 months of treatment
    patients
    5% of all patients studied discontinued treatment due to diarrhea events vs <1% of placebo-treated patients

    ALT, alanine aminotransferase; AST, aspartate aminotransferase; DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HRCT, high resolution computed tomography; IPF, idiopathic pulmonary fibrosis; SD, standard deviation; ULN, upper limit of normal.

    References

    1. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079-1087.

    2. Richeldi L, et al. N Engl J Med. 2014;370(22):2071-2082.

    3. Richeldi L, et al. N Engl J Med. 2011;365(12):1079-1087.

    4. OFEV® Local Summary of Product Characteristics, July 2024.

    5. Hilberg F, et al. Cancer Res. 2008;68(12):4774-4782.

    6. Wollin L, et al. J Pharmacol Exp Ther. 2014;349(2):209-220.

    7. Raghu G, et al. Am J Respir Crit Care Med. 2011;183(6):788-824.