ANORO delivers superior lung function improvement vs SPIRIVA HANDIHALER1,2

Trough FEV1 at Day 169

ANORO ELLIPTA is a combination anticholinergic/LABA for the maintenance treatment of airflow obstruction in patients with COPD.

SPIRIVA HANDIHALER is an anticholinergic for the maintenance treatment of bronchospasm associated with COPD, and for reducing COPD exacerbations.3

Studied in patients with moderate or worse COPD (GOLD 2-4).

In a separate study (DB2113374), ANORO ELLIPTA (n=217) compared with SPIRIVA HANDIHALER (n=215) showed a 60-mL difference* (208 mL and 149 mL, respectively), but due to testing hierarchy, statistical significance cannot be inferred.1

*Reflects rounding.

Description of Studies1,2,4

The efficacy and safety of a once-daily dose of ANORO ELLIPTA and SPIRIVA HANDIHALER (tiotropium bromide inhalation powder) were evaluated in 24-week, multicenter, randomized, blinded, active-controlled, double-dummy, parallel-group studies in patients (mean age range: 62 to 65 years) with COPD. At screening, patients had a mean postbronchodilator FEV1 range of 46.4% to 47.7% predicted.

Primary endpoint

Trough (predose) FEV1 at Day 169 (defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 168).

ANORO reduced rescue medication use vs SPIRIVA HANDIHALER1,2

Patients taking ANORO had fewer rescue albuterol puffs per day over 24 weeks compared with patients taking SPIRIVA HANDIHALER1,2,4

Other endpoint: Endpoint was not adjusted for multiplicity

Studied in patients with moderate or worse COPD (GOLD 2 or 3).

LS mean number of rescue albuterol puffs per day over Weeks 1 to 24: ANORO ELLIPTA=2.5, SPIRIVA HANDIHALER=3.2. Difference=0.7.

In ZEP117115, LS mean number of rescue albuterol puffs per day was 1.8 for ANORO ELLIPTA (n=454) and 2.3 for SPIRIVA HANDIHALER (n=451), which corresponds to a 0.5 difference or a 22% reduction. Other endpoint not adjusted for multiplicity.2,4

In DB2113374, as part of a predefined hierarchy, one comparison for the primary endpoint did not achieve statistical significance, and therefore subsequent comparisons are descriptive only. In this study, the LS mean number of rescue albuterol puffs per day for ANORO ELLIPTA (n=217) and SPIRIVA HANDIHALER (n=215) was 2.9 vs 3.5, respectively.1,4

Description of Studies

See description of studies above.

Other efficacy endpoint

Rescue albuterol use (puffs/day), Weeks 1 to 24.

Adverse events occurring in ≥3% of subjects in any of the 3 studies1,2,4

Range of adverse events across these studies (%)

Safety data are descriptive only. The studies were not powered to compare the safety profiles of the products.

COPD=chronic obstructive pulmonary disease; FEV1=forced expiratory volume in 1 second; GOLD=Global Initiative for Chronic Obstructive Lung Disease; LABA=long-acting beta2-adrenergic agonist; LS=least squares.

Indication for ANORO ELLIPTA

ANORO is for the once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. ANORO is NOT for the relief of acute bronchospasm or for asthma.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (and placebo) were: pharyngitis, 2% (<1%); sinusitis, 1% (<1%); lower respiratory tract infection, 1% (<1%); constipation, 1% (<1%); diarrhea, 2% (1%); pain in extremity, 2% (1%); muscle spasms, 1% (<1%); neck pain, 1% (<1%); and chest pain, 1% (<1%).
  • In addition to the 6-month efficacy trials with ANORO, a 12-month trial evaluated the safety of umeclidinium/vilanterol 125 mcg/25 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and more common than placebo) in subjects receiving umeclidinium/vilanterol 125 mcg/25 mcg were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuation of such agents, because they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (and placebo) were: pharyngitis, 2% (<1%); sinusitis, 1% (<1%); lower respiratory tract infection, 1% (<1%); constipation, 1% (<1%); diarrhea, 2% (1%); pain in extremity, 2% (1%); muscle spasms, 1% (<1%); neck pain, 1% (<1%); and chest pain, 1% (<1%).
  • In addition to the 6-month efficacy trials with ANORO, a 12-month trial evaluated the safety of umeclidinium/vilanterol 125 mcg/25 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and more common than placebo) in subjects receiving umeclidinium/vilanterol 125 mcg/25 mcg were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuation of such agents, because they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (and placebo) were: pharyngitis, 2% (<1%); sinusitis, 1% (<1%); lower respiratory tract infection, 1% (<1%); constipation, 1% (<1%); diarrhea, 2% (1%); pain in extremity, 2% (1%); muscle spasms, 1% (<1%); neck pain, 1% (<1%); and chest pain, 1% (<1%).
  • In addition to the 6-month efficacy trials with ANORO, a 12-month trial evaluated the safety of umeclidinium/vilanterol 125 mcg/25 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and more common than placebo) in subjects receiving umeclidinium/vilanterol 125 mcg/25 mcg were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuation of such agents, because they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

Important Safety Information for
INCRUSE ELLIPTA

CONTRAINDICATIONS

  • The use of INCRUSE ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have hypersensitivity to umeclidinium or any of the excipients.

WARNINGS AND PRECAUTIONS

  • INCRUSE ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • INCRUSE ELLIPTA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • If paradoxical bronchospasm occurs, discontinue INCRUSE ELLIPTA and institute alternative therapy.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in one 12-week and one 24-week clinical trial with INCRUSE ELLIPTA as monotherapy (and placebo) were: nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); pharyngitis, 1% (<1%); viral upper respiratory tract infection, 1% (<1%); cough, 3% (2%); arthralgia, 2% (1%); myalgia, 1% (<1%); upper abdominal pain, 1% (<1%); toothache, 1% (<1%); contusion, 1% (<1%); tachycardia, 1% (<1%). Other adverse reactions with INCRUSE ELLIPTA observed with an incidence <1% but more common than placebo included atrial fibrillation.
  • In addition to the two placebo-controlled clinical trials with INCRUSE ELLIPTA, a 12-month trial evaluated the safety of umeclidinium 125 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and exceeded that in placebo) in subjects receiving umeclidinium 125 mcg as monotherapy were: nasopharyngitis, upper respiratory tract infection, urinary tract infection, pharyngitis, pneumonia, lower respiratory tract infection, rhinitis, supraventricular tachycardia, supraventricular extrasystoles, sinus tachycardia, idioventricular rhythm, headache, dizziness, sinus headache, cough, back pain, arthralgia, pain in extremity, neck pain, myalgia, nausea, dyspepsia, diarrhea, rash, depression, and vertigo.
  • In addition to the adverse reactions reported in the umeclidinium monotherapy trials, adverse reactions reported in four 12-week trials with INCRUSE ELLIPTA in combination with an inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA), at an incidence of ≥1% and exceeding ICS/LABA alone, were oropharyngeal pain and dysgeusia.

DRUG INTERACTIONS

  • Avoid coadministration of INCRUSE ELLIPTA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.