TEXT: REEVALUATE ASTHMA RESCUE
HELP PREVENT ASTHMA EXACERBATIONS by concomitantly treating inflammation and symptoms
VO: Help prevent asthma exacerbations by concomitantly treating inflammation and symptoms.
BOTTOM TABS: BURDEN, INFLAMMATION, SABA AND ICS PHARMACOLOGY, WINDOW OF OPPORTUNITY, RECOMMENDATIONS, KEY CONSIDERATIONS, INTRODUCTION TO AIRSUPRA, EXACERBATION Study, LUNG FUNCTION Study
TEXT: WHAT IS THE BURDEN OF ASTHMA EXACERBATIONS?
VO: What is the burden of asthma exacerbations?
TEXT: ADULT ASTHMA ATTACKS AND ED VISITS (2011-2021)1-3
Having had 1 or more asthma attacks in the past 12 months among people with current asthma.1 †Crude rate per 10,000 population.2
ED=emergency department.
GRAPHICS: Adult Asthma Attacks and ED Visits graph appears. Data points build to create final graph.
VO: Despite advancements in asthma management and the availability of new treatment options, the rates of asthma exacerbations and ED visits in US adults have remained high.
TEXT: DIRECT COSTS OF ASTHMA-RELATED HEALTHCARE RESOURCE UTLIZATION4*†:
HOSPITALIZATION
cost ~$17,830 with an average stay of 4.2 days
EMERGENCY DEPARTMENT VISIT
cost ~$557
OUTPATIENT OFFICE VISIT
cost ~$104
Based on administrative claims data from patients with asthma ≥4 years old (N=1,005,522) from the IBM MarketScan Commercial and Medicaid Research Databases (January 1, 2010, to December 31, 2017). HCRU and costs were assessed for 12 months post-index date and were reported in standard 2017 dollars using the US Medical CPI.4 †Asthma-related unit costs were calculated by adjusting 2017 dollars to 2022 dollars using the US Medical CPI. The estimated mean costs per asthma-related hospitalization, ED visit, and outpatient visit were $15,286, $478, and $89, respectively in standard 2017 dollars.4
CPI=Consumer Price Index; ED=emergency department; HCRU=healthcare resource utilization.
VO: A retrospective, observational analysis that utilized administrative claims data from patients with asthma has shown that direct costs of asthma-related healthcare resource utilization, such as hospitalizations, ED visits, and outpatient office visits, continue to contribute to the substantial economic burden related to asthma.
GRAPHIC: Each cost component is magnified as it is mentioned in VO.
TEXT: WHAT IS THE ROLE OF INFLAMMATION IN ASTHMA?
VO: What is the role of inflammation in asthma?
TEXT: FLUCTUATING AIRWAY INFLAMMATION CAN LEAD TO SYMPTOMS AND AN UNPREDICTABLE ASTHMA EXACERBATION5-7
This graph is a hypothetical illustration. Adapted from Larsson K, et al. NPJ Prim Care Respir Med. 2020;30(1):25.
VO: Airway inflammation is central to asthma symptoms and exacerbations. In asthma, inflammation and symptoms fluctuate and can vary over time and in intensity.
GRAPHIC: Larsson graph builds from left to right.
VO: While anti-inflammatory maintenance therapies help manage baseline inflammation, unpredictable rises in inflammation can lead to breakthrough symptoms and exacerbations.
GRAPHIC: Airway appears after chart fully builds.
VO: During these periods of rising inflammation, airways narrow and lung function is decreased, making it increasingly difficult for a person to breathe.
TEXT: IS SABA-ONLY RESCUE ENOUGH?
SABA=short-acting β2-agonist.
VO: Is SABA-only rescue enough?
TEXT: HISTORICALLY, ASTHMA RESCUE INHALERS APPROVED IN THE UNITED STATES HAVE TREATED SYMPTOMS BUT NOT INFLAMMATION5,8
VO: For many years, asthma rescue options approved in the US have included SABA-only inhalers. SABAs are bronchodilators and treat bronchoconstriction by relaxing airway smooth muscle. While SABA inhalers treat symptoms, they do not address inflammation, leaving patients at risk of worsening symptoms and exacerbations.
GRAPHIC: Cross-section of airway appears with all anatomic layers highlighted and both SABA and ICS information showing. When SABA is mentioned, SABA information is magnified and only smooth muscle layer is highlighted.
VO: Inhaled corticosteroids, which have anti-inflammatory effects, reduce airway inflammation and enhance bronchodilation.
GRAPHIC: When inhaled corticosteroids are mentioned, ICS information is magnified, SABA information shrinks, and only inner airway layers are highlighted.
VO: Therefore, treatment with ICS is needed to address inflammation and help reduce the risk of an exacerbation.
GRAPHIC: Both SABA and ICS information is magnified, and all airway layers are highlighted again.
TEXT: IS THERE AN OPPORTUNITY TO NOT ONLY ADDRESS SYMPTOMS BUT ALSO INTERRUPT THE RISE IN INFLAMMATION LEADING UP TO AN EXACERBATION?
VO: Is there an opportunity to not only address symptoms but also interrupt the rise in inflammation leading up to an exacerbation?
TEXT: IS THERE A WINDOW OF OPPORTUNITY TO HELP PREVENT AN IMPENDING EXACERBATION BY TREATING INFLAMMATION AND SYMPTOMS CONCOMITANTLY?
Adapted from Tattersfield AE, et al. Am J Respir Crit Care Med. 1999;160(2):594-599.
Data for the rate of change in PEF, symptoms, and rescue use were standardized, with day -14 equal to 0% and day 0 equal to 100%. A severe asthma exacerbation was defined as an exacerbation that required oral corticosteroids as judged by the clinical investigator or an episode in which morning PEF fell by more than 30% from mean morning PEF during the last 10 days of the run-in period (baseline) on 2 consecutive days. PEF, symptoms, and β2-agonist use as rescue were studied in 425 severe exacerbations over 12 months in a double-blind, randomized, parallel-group study across 71 centers in 9 countries assessing over 800 patients aged 18 to 70 years old (FACET).13
ICS=inhaled corticosteroid; LABA=long-acting β2-agonist; PEF=peak expiratory flow.
VO: Here you see findings from the FACET study, an asthma exacerbation reduction study, which examined 852 patients treated with an ICS with or without a LABA. This work examined the pattern of peak expiratory flow decline, symptoms, and rescue use in the 425 exacerbations that occurred during the study.
GRAPHIC: PEF/symptoms/rescue use chart grows from left to right.
ADDITIONAL FOOTNOTE TEXT: Window is for illustrative purposes only and is not part of the published data set.
VO: As you can see, in the 10 days before the exacerbation was diagnosed, peak flow declined while symptoms and rescue use increased. Note that the values returned to pre-exacerbation or near pre-exacerbation levels over the subsequent 2 weeks. As asthma symptoms worsen prior to an exacerbation, patients increase their fast-acting bronchodilator use, which does not address the worsening inflammation if used alone without an ICS.
GRAPHIC: The left side highlights the days before exacerbation. A hollow circle animates highlighting the pre-exacerbation area of the chart. Additional footnote text appears. The circle and new footnote text disappear at VO "over 2 weeks.”
NEW HEADLINE TEXT: THERE MAY BE A WINDOW OF OPPORTUNITY TO HELP PREVENT AN EXACERBATION BY TREATING BOTH SYMPTOMS AND INFLAMMATION5,13
VO: There may be a window of opportunity to help prevent an exacerbation by treating both symptoms and inflammation.
TEXT: WHAT DO ASTHMA EXPERTS RECOMMEND?
VO: What do asthma experts recommend?
TEXT: NAEPP GUIDELINES AND THE GINA REPORT SUPPORT TREATING SYMPTOMS AND INFLAMMATION CONCOMITANTLY WITH RESCUE/RELIEVER THERAPY7,14
Key Recommendations in Patients ≥12 Years Old
The use of ICS-formoterol is not approved for maintenance and rescue therapy or for as-needed rescue only in the US. The recommendations for ICS-formoterol are based on clinical data evaluating the use of ICS-formoterol formulations and strengths not approved and not available in the US. †ICS-formoterol should not be used as the reliever by patients who are taking a different maintenance ICS-LABA.7,14
Note: not a complete list; full recommendations are available in references provided at the end of this presentation or by scanning QR codes above.
GINA=Global Initiative for Asthma; ICS=inhaled corticosteroid; LABA=long-acting β2-agonist; NAEPP=National Asthma Education and Prevention Program; SABA=short-acting β2-agonist.
VO: The rescue approach to treating asthma symptoms has changed over time.
The 2020 NAEPP Guidelines and the 2024 GINA Report support a rescue approach that treats both symptoms and inflammation. As you can see on the left, NAEPP supports this concept at Steps 2, 3, and 4 as preferred therapy, with concomitant as-needed SABA plus ICS listed as an option at Step 2 and ICS-formoterol maintenance and rescue recommended at Steps 3 and 4.
GRAPHIC: The NAEPP recommendations box fades in.
VO: Moving to the right, you can see that GINA supports this concept in Tracks 1 and 2, with ICS-formoterol the preferred reliever in Track 1 and recommendations for concomitant use of SABA plus ICS in Track 2. It's important to note that GINA no longer recommends SABA-only treatment of asthma.
GRAPHIC: The GINA recommendations box fades in.
VO: The use of ICS-formoterol is not approved for maintenance and rescue therapy or for as-needed rescue only in the US. The recommendations for ICS-formoterol are based on clinical data evaluating the use of ICS-formoterol formulations and strengths not approved and not available in the US.
GRAPHIC: QR codes fade in.
Please pause to scan the QR codes shown for the latest GINA Report and NAEPP Guidelines.
GRAPHIC: QR codes magnify.
TEXT: KEY CONSIDERATIONS
TEXT: Exacerbations continue to drive costly healthcare resource utilization.1-4
VO: In summary, despite advances in asthma management, exacerbations continue to drive costly healthcare resource utilization.
TEXT: Airway inflammation in asthma is variable and can put patients at risk.5,7
VO: Airway inflammation in asthma is variable and can put patients at risk of symptoms and exacerbations.
TEXT: A window of opportunity may exist to help prevent an exacerbation if symptoms and inflammation are treated concomitantly.5,13
VO: A window of opportunity may exist to help prevent an exacerbation if symptoms and inflammation are treated concomitantly.
TEXT: Treating both symptoms and inflammation with rescue therapy is supported by asthma experts.7,14
VO: Treating both symptoms and inflammation with rescue therapy is supported by asthma experts.
VO: This concludes the disease state portion of the video. Now, let’s transition to discussing a rescue inhaler option to consider adding to your formulary.
GRAPHIC: Dots animate per MOA video, then inhaler image appears.
TEXT: AIRSUPRA® (albuterol/budesonide) is the first and only FDA-approved albuterol/budesonide combination rescue inhaler and is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma aged ≥18 years.15,16
FDA=US Food and Drug Administration; ICS=inhaled corticosteroid; SABA=short-acting β2-agonist.
Please see Important Safety Information throughout this video.
VO: AIRSUPRA is a combination of albuterol, a beta2-adrenergic agonist, and budesonide, a corticosteroid, indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age and older.
AIRSUPRA is the first and only FDA-approved anti-inflammatory rescue containing a SABA and an ICS and is designed to treat both symptoms and inflammation.
GRAPHIC: SABA/ICS graphic appears.
TEXT: Recommended dosage of AIRSUPRA is albuterol 180 mcg and budesonide 160 mcg administered as 2 oral inhalations of AIRSUPRA (albuterol/budesonide 90 mcg/80 mcg), with no more than 6 doses (12 inhalations) in a 24-hour period.16
FDA=US Food and Drug Administration; ICS=inhaled corticosteroid; SABA=short-acting β2-agonist.
Please see Important Safety Information throughout this video.
VO: The recommended dosage of AIRSUPRA is albuterol 180 mcg and budesonide 160 mcg administered as 2 oral inhalations of AIRSUPRA (albuterol/budesonide 90 mcg/80 mcg), with no more than 6 doses (12 inhalations) in a 24-hour period.
TEXT: SELECT SAFETY INFORMATION
Contraindications: Hypersensitivity to albuterol, budesonide, or to any of the excipients
Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a marker of destabilization of asthma and requires evaluation of the patient and their treatment regimen
Paradoxical Bronchospasm: AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. Discontinue AIRSUPRA immediately and institute alternative therapy if paradoxical bronchospasm occurs. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister
Cardiovascular Effects: AIRSUPRA, like other drugs containing beta2 -adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, and/or other symptoms. If such effects occur, AIRSUPRA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. Therefore, AIRSUPRA, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
Please see additional Important Safety Information at the end of this video and full Prescribing Information, including Patient Information, available on this site.
VO: Before reviewing the clinical data, let’s focus on some select safety information:
Contraindications to using AIRSUPRA include hypersensitivity to albuterol, budesonide, or any of the excipients
Deterioration of asthma can occur acutely or chronically, so if a patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a marker of asthma destabilization
AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, AIRSUPRA should be discontinued immediately and alternative therapy instituted. When associated with inhaled formulations, it frequently occurs with the first use of a new canister
AIRSUPRA, like other drugs containing β2 -adrenergic agonists, can produce clinically significant cardiovascular effects in some patients and may need to be discontinued. AIRSUPRA should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
Please see additional Important Safety Information at the end of this video and full Prescribing Information, including Patient Information, available on this site.
TEXT: MANDALA DENALI
VO: Now, let’s cover key information from two pivotal Phase III studies in which AIRSUPRA was studied, MANDALA and DENALI.
TEXT: MANDALA: A HEAD-TO-HEAD TRIAL OF AIRSUPRA VS ALBUTEROL AS RESCUE THERAPY
Phase III, randomized, double-blind, multicenter, variable-length exacerbation study (≥24 weeks) in symptomatic patients ≥12 years old with moderate to severe asthma16,17
While patients 12 to 17 years old were included in MANDALA, AIRSUPRA is not approved in this age group; therefore, efficacy results are only presented for adults ≥18 years of age. Since albuterol/budesonide 180/80 mcg is not an approved dose, this presentation will not include results for this arm of the study.
Administered as 2 actuations, with each actuation delivering albuterol/budesonide 90/80 mcg for the 180/160-mcg arm, albuterol-budesonide 90/40 mcg for the 180/80-mcg arm, and albuterol 90 mcg for the albuterol-alone arm.17
ICS=inhaled corticosteroid.
VO: We’ll start with the MANDALA study, a Phase III, randomized, double-blind, multicenter, variable-length exacerbation study of at least 24 weeks’ duration in which AIRSUPRA was studied head-to-head versus albuterol as rescue therapy. MANDALA enrolled more than 3,000 symptomatic patients 12 years of age or older with moderate to severe asthma who were all taking ICS-based maintenance therapy.
GRAPHIC: TREATMENT ARMS graphic appears.
VO: The primary efficacy endpoint was the time to first severe asthma exacerbation. Key secondary endpoints included the annualized rate of severe exacerbations and the annualized total systemic corticosteroid dose.
While patients 12 to 17 years of age were included in MANDALA, AIRSUPRA is not approved in this age group; therefore, efficacy results are only presented for adults 18 years of age or older. Since albuterol/budesonide 180/80 mcg is not an approved dose, this presentation will not include results for this arm of the study.
GRAPHIC: PRIMARY ENDPOINT and KEY SECONDARY ENDPOINTS graphics appear.
TEXT: MANDALA: ADULT PATIENT POPULATION (n=2940)16
KEY INCLUSION CRITERIA16,17
≥1 severe asthma exacerbation in the previous year
Asthma maintenance therapy* for ≥3 months with stable dosing for ≥4 weeks prior to screening
Prebronchodilator FEV1 of ≥40% and <90% of predicted normal and confirmed reversibility to albuterol
PATIENTS ENROLLED IN MANDALA16,18
Majority female and predominantly Caucasian
Mean prebronchodilator % predicted FEV1 of 63% with a mean % reversibility of 28%
80% of patients had 1 severe exacerbation in the prior year with 20% of patients having more than 1
Patients continued their maintenance therapy throughout the trial
Patients reported taking their maintenance therapy, on average, 75.4% of days19
Medium- to high-dose ICS or low- to high-dose ICS/LABA with or without an additional controller: LTRA, LAMA, or xanthines.
FEV1=forced expiratory volume in 1 second; ICS=inhaled corticosteroid; LABA=long-acting β2-agonist; LAMA=long-acting muscarinic antagonist; LTRA=leukotriene receptor antagonist.
VO: To participate in MANDALA, patients had to have one or more severe asthma exacerbations in the previous year. In addition, patients must have been on asthma maintenance therapy for at least 3 months, with stable dosing for 4 or more weeks prior to screening. Required maintenance therapy included medium- to high-dose ICS or low- to high-dose ICS/LABA, with or without an additional controller. Lastly, patients must have a prebronchodilator FEV1 between 40% and less than 90% of predicted normal with confirmed reversibility to albuterol.
Patients enrolled in MANDALA were predominantly female and Caucasian. Mean prebronchodilator percent predicted FEV1 was 63% with a mean reversibility of 28%. 80% of patients had one severe exacerbation in the prior year with 20% of patients having more than one.
During the study, patients continued taking their maintenance therapy. Patients reported taking their maintenance therapy, on average, 75.4% of days. Adherence was similar between treatment arms.
GRAPHIC: Inclusion criteria and patient enrollment bullets appear as each is mentioned in VO. Maintenance therapy bars appear on right.
TEXT: PRIMARY ENDPOINT16,17
Time to first severe asthma exacerbation
VO: The primary endpoint was time to first severe asthma exacerbation.
GRAPHIC: Endpoints graphic appears with PRIMARY ENDPOINT information highlighted.
TEXT: STATISTICALLY SIGNIFICANT REDUCTION IN EXACERBATION RISK VS ALBUTEROL16
Primary endpoint: Time to first exacerbation*
Data shown for AIRSUPRA 180/160 mcg and albuterol 180 mcg are for patients ≥18 years old.16 Data are from the pre-planned on-treatment efficacy analysis and included data collected while on randomized treatment prior to treatment discontinuation or change in maintenance therapy with censoring of data at the time of discontinuation or change in therapy.17
As measured by time to first severe exacerbation and adjusted for age group, region, and number of prior severe exacerbations in the 12 months before screening. An asthma exacerbation was considered severe if it resulted in at least 1 of the following: a temporary bolus/burst of SCS for at least 3 consecutive days to treat symptoms of asthma worsening (a single depo-injectable dose of corticosteroids was considered equivalent), an ED or urgent care visit due to asthma that required SCS, or an in-patient hospitalization due to asthma.17 †Curve truncated when <1% of patient population remained at risk.16 ‡Type I error was controlled for comparison of AIRSUPRA 180/160 mcg dose with albuterol with the Hochberg procedure.17 §Subject-based NNT.20
CI=confidence interval; ED=emergency department; HR=hazard ratio; NNT=number needed to treat; SCS=systemic corticosteroid.
VO: When compared head-to-head vs albuterol, AIRSUPRA showed a statistically significant reduction in the risk of severe asthma exacerbations by 28% when used as needed for rescue therapy in response to symptoms.
GRAPHIC: Time to First Severe Exacerbation Chart appears. 28% reduction graphic and text appear when mentioned in VO.
VO: The subject-based NNT to prevent one additional person having a severe exacerbation in patients 18 years of age or older with AIRSUPRA was 14 compared with the albuterol group. Therefore, 14 patients need to be treated with AIRSUPRA for 1 year to prevent one additional person from having a severe exacerbation.
GRAPHIC: NNT box appears.
TEXT: KEY SECONDARY ENPOINTS16,17
Annualized rate of severe exacerbations
Annualized total systemic corticosteroid dose
VO: As mentioned earlier, two of the secondary endpoints from MANDALA were the annualized rate of severe exacerbations and the annualized total systemic corticosteroid dose.
GRAPHIC: Endpoints graphic appears with KEY SECONDARY ENDPOINTS information highlighted.
TEXT: STATISTICALLY SIGNIFICANT REDUCTION IN ANNUALIZED EXACERBATION RATE VS ALBUTEROL16
Key secondary endpoint: Annualized rate of severe exacerbations*†
Data shown for AIRSUPRA 180/160 mcg and albuterol 180 mcg are for patients ≥18 years old.16 Data are from the pre-planned on-treatment efficacy analysis and included data collected while on randomized treatment prior to treatment discontinuation or change in maintenance therapy with censoring of data at the time of discontinuation or change in therapy.17 Secondary endpoints were controlled using a hierarchical testing sequence between all treatment comparisons, grouped by endpoint.17
An asthma exacerbation was considered severe if it resulted in at least 1 of the following: a temporary bolus/burst of SCS for at least 3 consecutive days to treat symptoms of asthma worsening (a single depo-injectable dose of corticosteroids was considered equivalent), an ED or urgent care visit due to asthma that required SCS, or an in-patient hospitalization due to asthma.17 †Annualized severe asthma exacerbation rates were adjusted for age, region, and number of severe exacerbations in the 12 months before screening and time at risk.17 There were 324 severe exacerbations in patients treated with AIRSUPRA and 403 in patients treated with albuterol.16
CI=confidence interval; ED=emergency department; RR=risk ratio; SCS=systemic corticosteroid.
VO: For the annualized rate of severe exacerbations, AIRSUPRA demonstrated a statistically significant reduction of 24% compared with albuterol. There were 324 severe exacerbations in patients treated with AIRSUPRA compared to 403 severe exacerbations in patients treated with albuterol.
GRAPHIC: Severe Exacerbation Rate graph and 24% Reduction graphic and text animate onscreen.
TEXT: STATISTICALLY SIGNIFICANT DIFFERENCE IN ANNUALIZED SCS DOSE VS ALBUTEROL (P=0.001)16,21
Key secondary endpoint: Annualized total SCS dose21
Data shown for AIRSUPRA 180/160 mcg and albuterol 180 mcg are for patients ≥18 years old.16 Data are from the pre-planned on-treatment efficacy analysis and included data collected while on randomized treatment prior to treatment discontinuation or change in maintenance therapy with censoring of data at the time of discontinuation or change in therapy.17 Secondary endpoints were controlled using a hierarchical testing sequence between all treatment comparisons, grouped by endpoint.17
Mean annualized doses of SCS were rounded to the nearest whole number in the AIRSUPRA Prescribing Information.16
Prednisone equivalent.21
SCS=systemic corticosteroid.
VO: The annualized total SCS dose due to asthma was calculated for each patient during the study period. There was a statistically significant difference in annualized total SCS dose with AIRSUPRA compared to albuterol, with a 32% reduction in mean annualized dose per patient.
GRAPHIC: Mean Total Annualized SCS Dose graph and 32% Reduction graphic and text animate onscreen.
TEXT: SAFETY PROFILE SIMILAR TO ALBUTEROL REGARDLESS OF BACKGROUND ICS DOSE16
Data shown are for patients ≥12 years old. AIRSUPRA is not approved for patients 12 to 17 years of age.
Oral candidiasis also includes those reactions reported under the preferred term oropharyngeal candidiasis.
ICS=inhaled corticosteroid.
VO: Now let’s look at the safety profile from MANDALA. Adverse reactions reported in 1% or more of patients who used as-needed AIRSUPRA in MANDALA included headache (4.3%), oral candidiasis (1.3%), and cough (1%) compared to 4.9%, 0.5%, and 1.1%, respectively in the as-needed albuterol group. Note that in MANDALA, the safety profile of AIRSUPRA was similar to that of albuterol regardless of background ICS dose. Data shown are for patients 12 years of age or older. AIRSUPRA is not approved for patients 12 to 17 years of age.
GRAPHIC: Table appears.
TEXT: DENALI: A LUNG FUNCTION STUDY IN PATIENTS WITH MILD TO MODERATE ASTHMA16
Phase III, randomized, double-blind, active-comparator and placebo-controlled lung function study conducted over 12 weeks16,22
While patients 12 to 17 years of age were included in DENALI, AIRSUPRA is not approved in this age group; therefore, efficacy results are only presented for adults ≥18 years of age. Since albuterol/budesonide 180/80 mcg is not an approved dose, this presentation will not include results for this arm of the study. AIRSUPRA is not indicated or approved for maintenance use.
Patients used sponsor-provided albuterol as needed in response to symptoms during the treatment period.22 †Doses consisted of two inhaler actuations, with each actuation delivering albuterol/budesonide 90/80 mcg for the 180/160-mcg arm, albuterol/budesonide 90/40 mcg for the 180/80-mcg arm, budesonide 80 mcg for the budesonide-alone arm, and albuterol 90 mcg for the albuterol-alone arm.22
ICS=inhaled corticosteroid; QID=four times daily; SABA=short-acting β2-agonist.
VO: AIRSUPRA was also studied in the DENALI trial, a Phase III, randomized, double-blind, active-comparator, placebo-controlled lung function study conducted over 12 weeks that evaluated the efficacy and safety of AIRSUPRA compared to albuterol, budesonide, and placebo.
The DENALI study was conducted in 989 patients 12 years of age and older with mild to moderate asthma. Patients were previously treated with as-needed SABA only or with low-dose ICS maintenance plus as-needed SABA.
While patients 12 to 17 years of age were included in DENALI, AIRSUPRA is not approved in this age group; therefore, efficacy results are only presented for adults 18 years of age or older. Since albuterol/budesonide 180/80 mcg is not an approved dose, this presentation will not include results for this arm of the study. Additionally, AIRSUPRA is not indicated or approved for maintenance use.
GRAPHIC: Treatment arms graphic appears.
TEXT: DENALI: ADULT PATIENT POPULATION (n=964)16
KEY INCLUSION CRITERIA22,23
Previously treated with one of the following:
— As-needed SABA only
— Stable low-dose ICS in addition to as-needed SABA
Prebronchodilator FEV1 of ≥50% and <85% predicted normal value for adults
Reversibility in FEV1 (≥15% increase compared to baseline)
PATIENTS ENROLLED IN DENALI16,18
Majority female and predominantly Caucasian
Mean prebronchodilator % predicted FEV1 of 65% with a mean % reversibility of 29%
Pre-study background therapy did not include ICS for 52% of patients while 48% were taking ICS
FEV1=forced expiratory volume in 1 second; ICS=inhaled corticosteroid; SABA=short-acting β2-agonist.
VO: To participate in DENALI, patients needed to be previously treated with as-needed SABA only, or stable low-dose ICS in addition to as-needed SABA. In addition, patients had to have a prebronchodilator FEV1 between 50% and less than 85% of predicted normal with confirmed reversibility to albuterol. Patients enrolled in DENALI were predominantly female and Caucasian. Mean prebronchodilator percent predicted FEV1 was 65% with a mean reversibility of 29%. 48% of patients were on pre-study ICS background therapy while 52% were not on ICS-containing therapy.
TEXT: PROFILES OF AIRSUPRA AND ALBUTEROL WERE SIMILAR IN TERMS OF ONSET AND DURATION OF FEV1 RESPONSE16
ONSET* AND DURATION† OF BRONCHODILATION‡
Data were not evaluated for statistical significance and results are descriptive only.
Efficacy data shown for AIRSUPRA 180/160 mcg and albuterol 180 mcg are for patients ≥18 years old.16
Time to onset was defined as the time from dose to the first instance at which a response (≥15% increase in FEV1 post-dose within 30 minutes on Day 1) was observed.23 †Duration was defined as the continual period in which the response (≥15% increase in FEV1 post-dose within 30 minutes on Day 1) was observed.23 ‡Data shown only for patients who had a response to AIRSUPRA 180/160 mcg or albuterol 180 mcg following a single dose on Day 1 (51% and 43% of patients for AIRSUPRA and albuterol, respectively).16
FEV1=forced expiratory volume in 1 second.
VO: The DENALI study showed that the profiles of AIRSUPRA and albuterol were similar in terms of onset of bronchodilation and duration of FEV1 response. In DENALI, onset of bronchodilation was defined by a ≥15% increase in FEV1 post dose within 30 minutes on Day 1. Among patients who had a response in FEV1, the median time to onset of bronchodilation was 7.5 minutes with AIRSUPRA and 10 minutes with albuterol.
GRAPHIC: Onset (median) chart appears and animates on the left.
VO: Following a single dose on Day 1, the mean duration of bronchodilation was 186.9 minutes with AIRSUPRA 180/160 mcg and 167.9 minutes with albuterol 180 mcg, respectively.
GRAPHIC: Duration (mean) chart appears and animates on the right.
NEW FOOTNOTE TEXT: Data were not evaluated for statistical significance and results are descriptive only.22
VO: Data were not evaluated for statistical significance and results are descriptive only.
GRAPHIC: New footnote text appears.
TEXT: SUMMARY OF ADVERSE REACTIONS* REPORTED IN ≥1% OF PATIENTS WHO USED AIRSUPRA
Data shown are for patients ≥12 years old. AIRSUPRA is not approved for patients 12 to 17 years of age. AIRSUPRA is not indicated or approved for maintenance use.
Adverse reactions for AIRSUPRA 180/160 mcg with an incidence ≥1% that exceeded the incidence in MANDALA.16
QID=4 times a day.
VO: Adverse reactions for AIRSUPRA observed in DENALI were similar to those in MANDALA. Here is a summary of adverse reactions that were reported in 1% or more of patients in DENALI and that exceeded the incidence in MANDALA. As you can see, the adverse reactions reported for AIRSUPRA included headache (5.1%), dysphonia (2.0%), and oral/oropharyngeal candidiasis (1.5%) compared to 7.1%, 0%, and 0%, respectively in the placebo arm.
Data shown are for patients 12 years of age and older. AIRSUPRA is not approved for patients 12 to 17 years of age.
Additionally, AIRSUPRA is not indicated or approved for maintenance use.
GRAPHIC: DENALI adverse reaction table lands.
TEXT: INCLUDE AIRSUPRA ON YOUR FORMULARY FOR PATIENTS WITH ASTHMA
The first and only FDA-approved albuterol/budesonide combination rescue inhaler that is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma aged ≥18 years.15,16
IN A HEAD-TO-HEAD STUDY VS ALBUTEROL:
FDA=US Food and Drug Administration.
VO: AIRSUPRA is the first and only FDA-approved albuterol/budesonide combination rescue inhaler and is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma 18 years of age or older.
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VO: In the MANDALA study, when compared to albuterol as rescue therapy, AIRSUPRA demonstrated a significant reduction in the risk of severe exacerbation, a significant reduction in the annualized rate of severe exacerbations, and a significant difference in the annualized total SCS dose, with a reduction in mean annualized dose per patient.
The most common adverse reactions with AIRSUPRA include headache, oral candidiasis, cough, and dysphonia.
For your patient population with asthma, include AIRSUPRA on your formulary.
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TEXT: AIRSUPRA IMPORTANT SAFETY INFORMATION (CONT'D)
Do Not Exceed Recommended Dose: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
Hypersensitivity Reactions, Including Anaphylaxis: Can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA, as demonstrated by cases of anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria. Discontinue AIRSUPRA if such reactions occur
Risk of Sympathomimetic Amines with Certain Coexisting Conditions: AIRSUPRA, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines
Hypokalemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients. The decrease in serum potassium is usually transient, not requiring supplementation
Immunosuppression and Risk of Infections: Due to possible immunosuppression from the use of inhaled corticosteroids (ICS), potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
Oropharyngeal Candidiasis: Has occurred in patients treated with ICS agents. Monitor patients periodically. Advise patients to rinse his/her mouth with water, if available, without swallowing after inhalation
Hypercorticism and Adrenal Suppression: May occur with very high doses in susceptible individuals. If such changes occur, consider appropriate therapy
Reduction in Bone Mineral Density: Decreases in bone mineral density have been observed with long-term administration of ICS. For patients at high risk for decreased bone mineral density, assess initially and periodically thereafter
Glaucoma and Cataracts: Have been reported following the long-term administration of ICS, including budesonide, a component of AIRSUPRA
Effects on Growth: Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population
Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, and dysphonia
Drug Interactions: AIRSUPRA should be administered with caution to patients being treated with:
Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
Short-acting bronchodilators (concomitant use of additional beta-agonists with AIRSUPRA should be used judiciously to prevent beta-agonist overdose)
Beta-blockers (may block pulmonary effects of beta-agonists and produce severe bronchospasm)
Diuretics or non-potassium-sparing diuretics (may potentiate hypokalemia or ECG changes). Consider monitoring potassium levels
Digoxin (may decrease serum digoxin levels). Consider monitoring digoxin levels
Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants (Use AIRSUPRA with extreme caution; may potentiate effect of albuterol on the cardiovascular system)
Use AIRSUPRA with caution in patients with hepatic impairment, as budesonide systemic exposure may increase. Monitor patients with hepatic disease
Please see full Prescribing Information, including Patient Information, available on this site.
VO: To complete the description of AIRSUPRA, please see additional Important Safety Information onscreen:
Patients should not exceed the recommended dose: clinically significant cardiovascular effects and fatalities have been reported in association with excess use of inhaled sympathomimetic drugs
Hypersensitivity reactions, including anaphylaxis: can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA. Discontinue AIRSUPRA if the reactions shown onscreen occur
AIRSUPRA should be used with caution in patients with certain coexisting conditions, such as convulsive disorders, hyperthyroidism, or diabetes mellitus, and in patients who are unusually responsive to sympathomimetic amines
Significant hypokalemia may occur in some patients from use of beta-adrenergic agonists, and
Possible immunosuppression and potential worsening of infections from the use of inhaled corticosteroids (ICS) could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
Additional Important Safety Information includes:
Oropharyngeal candidiasis has occurred in patients treated with ICS agents; advise patients to rinse their mouth with water, if available
Hypercorticism and adrenal suppression may occur with very high doses in susceptible individuals
Reduction in bone mineral density has been observed and glaucoma and cataracts have been reported with long-term administration of ICS
Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients; however, note the safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population
Further Important Safety Information includes:
The most common adverse reactions reported for AIRSUPRA with an incidence of greater than or equal to 1% were headache, oral candidiasis, cough, and dysphonia
AIRSUPRA should be administered with caution to patients being treated with:
Strong cytochrome P450 3A4 inhibitors, short-acting bronchodilators, beta-blockers, diuretics or non-potassium-sparing diuretics, digoxin, monoamine oxidase inhibitors or tricyclic antidepressants
Use AIRSUPRA with caution in patients with hepatic impairment, as budesonide systemic exposure may increase. Monitor patients with hepatic disease.
Please see the full Prescribing Information, including Patient Information, available on this site.
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TEXT: REFERENCES:
1. Centers for Disease Control and Prevention. Asthma data visualizations. Accessed July 30, 2024. https://www.cdc.gov/asthma/data-visualizations/default.htm. 2. Centers for Disease Control and Prevention. Most recent national asthma data. Accessed July 30, 2024. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. 3. Centers for Disease Control and Prevention. Asthma emergency department (ED) visits 2010–2018. Accessed July 30, 2024. https://archive.cdc.gov/#/details?url=https://www.cdc.gov/asthma/asthma_stats/asthma-ed-visits_2010-2018.html. 4. Data on File, REF-202607. AstraZeneca Pharmaceuticals LP. 5. Larsson K, Kankaanranta H, Janson C, et al. Bringing asthma care into the twenty-first century. NPJ Prim Care Respir Med. 2020;30(1):25. doi:10.1038/s41533-020-0182-2. 6. Frey U, Suki B. Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment, and disease progression and control. Lancet. 2008;372(9643):1088-1099. doi:10.1016/S0140-6736(08)61450-6. 7. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2024. Accessed July 30, 2024. https://ginasthma.org. 8. O’Byrne PM, Jenkins C, Bateman ED. The paradoxes of asthma management: time for a new approach? Eur Respir J. 2017;50(3):1701103. doi:10.1183/13993003.01103-2017. 9. Amrani Y, Bradding P. β2-Adrenoceptor function in asthma. Adv Immunol. 2017;136:1-28. doi:10.1016/bs.ai.2017.06.003. 10. Bossé Y, Riesenfeld EP, Paré PD, Irvin CG. It’s not all smooth muscle: non-smooth-muscle elements in control of resistance to airflow. Annu Rev Physiol. 2010;72:437-462. doi:10.1146/annurev-physiol-021909-135851. 11. Koziol-White C, Johnstone TB, Corpuz ML, et al. Budesonide enhances agonist-induced bronchodilation in human small airways by increasing cAMP production in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2020;318(2):L345-L355. doi:10.1152/ajplung.00393.2019. 12. Alangari AA. Genomic and non-genomic actions of glucocorticoids in asthma. Ann Thorac Med. 2010;5(3):133-139. doi:10.4103/1817-1737.65040. 13. Tattersfield AE, Postma DS, Barnes PJ, et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group. Am J Respir Crit Care Med. 1999;160(2):594-599. doi:10.1164/ajrccm.160.2.9811100. 14. Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the Asthma Management Guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217-1270. doi:10.1016/j.jaci.2020.10.003. 15. U.S. Food and Drug Administration. FDA approves drug combination treatment for adults with asthma. Accessed July 30, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-combination-treatment-adults-asthma. 16. AIRSUPRA® (albuterol/budesonide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 17. Papi A, Chipps BE, Beasley R, et al. Albuterol-budesonide fixed-dose combination rescue inhaler for asthma. N Engl J Med. 2022;386(22):2071-2083. doi:10.1056/NEJMoa2203163. 18. Data on File, REF-174347. AstraZeneca Pharmaceuticals LP. 19. Data on File, REF-202630. AstraZeneca Pharmaceuticals LP. 20. Data on File, REF-187434. AstraZeneca Pharmaceuticals LP. 21. Data on File, REF-197604. AstraZeneca Pharmaceuticals LP. 22. Chipps BE, Israel E, Beasley R, et al. Albuterol-budesonide pressurized metered dose inhaler in patients with mild-to-moderate asthma: results of the DENALI double-blind randomized controlled trial. Chest. 2023;164(3):585-595. doi:10.1016/j.chest.2023.03.035. 23. A study to assess the efficacy and safety of budesonide/albuterol metered dose inhaler (BDA MDI/PT027) used 4 times daily in adults and children 4 years of age or older with asthma (DENALI). ClinicalTrials.gov identifier: NCT03847896. Accessed July 30, 2024. https://clinicaltrials.gov/ct2/show/NCT03847896.
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