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UK-RES-2000248 Feb 2020

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UK-RES-2000003 Jan 2020

INTENDED FOR UK HEALTHCARE PROFESSIONALS
Fostair® logo (beclometasone/formoterol) Extrafine formulation 100/6 & 200/6
Background

Fostair in Adult Asthma
Evidence Summary

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The following Fostair evidence summary provides you with information that will assist in your prescribing decision.
Mechanisms of action and pharmacodynamic effects

Fostair contains beclometasone dipropionate and formoterol. These two active ingredients have different modes of action. Like other inhaled corticosteroids and beta2-agonist combinations, additive effects are seen in respect of reduction in asthma exacerbations.1

Beclometasone dipropionate
Beclometasone dipropionate given by inhalation at recommended doses has a glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma with less adverse effects than when corticosteroids are administered systemically.1

Formoterol
Formoterol is a selective beta2-adrenergic agonist that produces relaxation of bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect sets in rapidly, within 1–3 minutes after inhalation, and has a duration of 12 hours after a single dose.1

Fostair pMDI 100/6

Adult asthma

Clinical efficacy for Fostair maintenance therapy

In clinical trials in adults, the addition of formoterol to beclometasone dipropionate improved asthma symptoms and lung function and reduced exacerbations.1

In a 24-week study the effect on lung function of Fostair was at least equal to that of the free combination of beclometasone dipropionate and formoterol and exceeded that of beclometasone dipropionate alone.1

Clinical efficacy for Fostair maintenance and reliever therapy

In a 48-week parallel group study involving 1,701 asthma patients, the efficacy of Fostair administered as maintenance (1 inhalation b.d.) and reliever therapy (up to a total of 8 puffs per day) was compared to Fostair administered as maintenance therapy (1 inhalation b.d.) plus as needed salbutamol, in adult patients with un-controlled moderate to severe asthma. The results demonstrated that Fostair used as maintenance and reliever therapy significantly prolonged the time to first severe exacerbation (*) when compared with Fostair used as maintenance plus as needed salbutamol (p<0.001 for both ITT and PP population). The rate of severe asthma exacerbations per patients/year, was significantly reduced in the maintenance and reliever therapy group compared to salbutamol group: 0.1476 vs. 0.2239 respectively (statistically significant reduction: p<0.001). Patients in the Fostair maintenance and reliever group achieved a clinically meaningful improvement in asthma control. The mean number of inhalations/day of reliever medication and the proportion of patients using reliever medication decreased similarly in both groups.1

Note* : severe exacerbations were defined as deterioration in asthma resulting in hospitalisation or emergency room treatment or resulting in the need for systemic steroids for more than 3 days.

In another clinical study, a single dose of Fostair 100/6 mcg provided a quick bronchodilation effect and a rapid relief from dyspnoea symptoms similar to that of salbutamol 200 micrograms/dose in asthmatic patients when metacholine challenge is used to induce bronchoconstriction.1

Fostair NEXThaler 100/6

The efficacy of the two components of Fostair NEXThaler inhalation powder has been assessed in three separate studies in comparison with the 100 micrograms/6 micrograms pressurised inhalation solution formulation in moderate to severe patients with persistent asthma. Overall, the efficacy of the two inhalers is expected to be equivalent in clinical practice at both 1 and 2 inhalations b.d.2

In one study the primary objective was the efficacy evaluation of the inhaled corticosteroid component measured on bronchodilation (pre-dose FEV1). A clinically significant improvement in pre-dose FEV1 was seen in 696 patients with moderate to severe symptomatic asthma at the end of a 3 months treatment period in comparison with baseline values, with 1 inhalation b.d. and 2 inhalations b.d. of both formulations. A mean increase of at least 250 mL was observed. There was no clinically relevant difference in pre-dose FEV1 between Fostair NEXThaler inhalation powder and the pressurised inhalation solution at either dosage. A significant dose-response was observed for morning PEF. Statistical significance for the dose-response in pre-dose FEV1 was not reached. Measurements of control of asthma such as morning and evening asthma symptoms scores and percentage of days without symptoms improved significantly from baseline through to the end of the treatment period, particularly for the two high doses of both formulations.2

In the second study the primary aim was the efficacy evaluation on the long-acting β2-agonist component of Fostair NEXThaler. In this study bronchodilation at the onset and up to 12 hours after single doses administration was measured by serial spirometric evaluations of FEV1 (FEV1 AUC over at least 80% of formoterol duration of action). Compared with placebo, Fostair NEXThaler, one inhalation and four inhalations of both active ingredients significantly improved the FEV1 AUC0–12.. Both doses of Fostair NEXThaler inhalation powder were non-inferior to the corresponding dose of the pressurised inhalation solution formulation. A statistically significant dose-response was found with both formulations between the low and high dose.2

In the third study, after a 4-week run-in period with beclometasone dipropionate/formoterol pressurised inhalation solution fixed combination, 1 inhalation b.d., 755 controlled asthmatic patients were randomised to 8 weeks of treatment with the same inhaler, with Fostair NEXThaler inhalation powder or with beclometasone dipropionate 100 micrograms per dose inhalation powder, all given at 1 inhalation b.d. The primary objective was the change from baseline over the entire treatment period in mean morning expiratory flow (PEF). After 8 weeks of treatment there was no difference in the primary endpoint between the two combination inhalers, both being significantly better than beclometasone dipropionate monotherapy. No differences were found between the two combination inhalers in measures of symptoms such as the asthma control questionnaire score and the number of rescue-free days.2

Fostair pMDI 200/6

The efficacy of Fostair 200/6, 2 puffs twice a day, was evaluated in a 12 week pivotal trial comparing the effect on lung function versus treatment with beclometasone dipropionate monotherapy in asthmatic patients not adequately controlled with previous treatment (high dose ICS or medium dose-ICS+LABAs combinations). The study demonstrated the superiority of Fostair 200/6 compared to BDP in terms of change from baseline in the average pre-dose morning PEF (adjusted mean difference 18.53 L).3

In a 24 week pivotal trial the safety profile of Fostair 200/6, 2 puffs twice a day, was comparable to that of an approved fixed dose combination (fluticasone/salmeterol 500/50, 1 puff twice daily). No clinically relevant effect was observed with Fostair 200/6 on the HPA axis after 6 months of treatment. The study showed that both Fostair 200/6 micrograms and the approved fixed dose combination were not superior to non extrafine beclometasone dipropionate monotherapy (2000 micrograms /day) on the change in pre-dose morning FEV1 and percentage of complete days without asthma symptoms.3

Fostair NEXThaler 200/6

In a double blind, randomised, 5-way crossover, placebo controlled study in 60 partially controlled or uncontrolled adult asthmatic patients with two different single doses (1 or 4 inhalations) of Fostair NEXThaler 100 micrograms/6 micrograms and Fostair NEXThaler 200 micrograms/6 micrograms, or placebo, the bronchodilator effect (FEV1 AUC0–12h normalised by time) was investigated. The adjusted mean difference (95% CI) for Fostair NEXThaler 200 micrograms/6 micrograms vs. Fostair NEXThaler 100 micrograms/6 micrograms was 0.029 (-0.018; 0.076) L for the lower formoterol dose level (1 inhalation – 6 micrograms) and 0.027 (-0.020; 0.073) L for the higher formoterol dose level (4 inhalations – 24 micrograms). The results showed that the lower limits of the two-sided 95% CIs for the adjusted mean difference between treatments were well above the pre-specified non-inferiority limit (-0.12 L) thus demonstrating the predefined non-inferiority (0.12 L) of Fostair NEXThaler 200 micrograms/6 micrograms compared to the lower strength in terms of FEV1 AUC0–12h normalised by time at both formoterol dose levels (6 and 24 micrograms).4

Study methods

Usability study with 66 adult patients with asthma with no previous experience of using a DPI, randomised crossover comparison with 3 devices.

The main measures were number of steps failed for each device, number of people who were able to use the device successfully, the time it took to set up the device, the time to read the instructions and patient preferences.

Fostair NEXThaler was preferred by patients with asthma vs. Symbicort® Turbohaler® and Seretide® Accuhaler®5

Bar chart % of responses - 75.4% Fostair NEXThaler - 7.7% Symicort® Turbohaler - 16.9% Seretide® Accuhaler

Response to question: OVERALL, if you had to pick one of the inhalers to use every day (assuming the drug is the same in each), which one would you be most likely to choose?5

Among patients prescribed a Dry Powder Inhaler (DPI) to help treat their asthma symptoms, inhaler mishandling is a common issue and often leads to poor clinical outcomes.5 Voshaar et al investigated this by looking at the usability characteristics of Fostair NEXThaler against two other DPIs; Symbicort® Turbohaler® and Seretide® Accuhaler®.

The results showed that Fostair NEXThaler was superior to the two other DPIs with regards to the number of device use failures, time to set up and time to read the instructions for use (p<0.001). Patients also rated Fostair NEXThaler as the easiest to use and most preferred inhaler to their own, as shown in the graph.

Symbicort® and Turbohaler® are registered trademarks of AstraZeneca AB Limited. Seretide® and Accuhaler® are registered trademarks of the GlaxoSmithKline Group of Companies.

AUC: area under curve; b.d.: twice daily; BDP: beclometasone dipropionate; CI: confidence interval; DPI: dry powder inhaler; FEV1: forced expiratory volume in 1 second; HPA: hypothalamic-pituitary-adrenal; ICS: inhaled corticosteroid; ITT: intention-to-treat; LABA: long-acting β2-agonist; PEF: peak expiratory flow; pMDI: pressurised metered dose inhaler; PP: per protocol.

References:
1. Fostair pMDI 100/6 Summary of Product Characteristics. Chiesi Limited.
2. Fostair NEXThaler 100/6 Summary of Product Characteristics. Chiesi Limited.
3. Fostair pMDI 200/6 Summary of Product Characteristics. Chiesi Limited.
4. Fostair NEXThaler 200/6 Summary of Product Characteristics. Chiesi Limited.
5. Voshaar T, et al. J Aerosol Med Pulm Drug Deliv. 2014; 27(5): 363–370.

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Chiesi Ltd on 0800 0092329 (UK), 1800 817459 (IE) PV.UK@Chiesi.com.