Budesonide-Glycopyrronium-Formoterol Fumarate Dihydrate (Breztri Aerosphere)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses budesonide-glycopyrronium (as bromide)-formoterol fumarate dihydrate, pressurized inhalation aerosol for oral inhalation (Breztri Aerosphere) (182 mcg/8.2 mcg/5.8 mcg per metered actuation) Indication: Indicated for the long-term maintenance treatment to reduce exacerbations of COPD and treat airflow obstruction to relieve symptoms in patients with COPD, including chronic bronchitis and/or emphysema, who are not adequately treated by a combination of an ICS-LABA or a combination of a LAMA-LABA

A scintigraphy study of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in patients with moderate-to-very severe chronic obstructive pulmonary disease

Background Triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2-agonists (ICS/LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD. Methods This phase I, single-dose, open-label gamma scintigraphy imaging study (NCT03906045) was conducted in patients with moderate-to-very severe COPD. Patients received two actuations of BGF MDI (160/9/4.8 μg per actuation) radiolabeled with technetium‑99‑pertechnetate, not exceeding 5 MBq per actuation. Immediately following each inhalation, patients performed a breath-hold of up to 10 s, then exhaled into an exhalation filter. Gamma scintigraphy imaging of the anterior and posterior views of the lungs and stomach, and a lateral head and neck view, were performed immediately after exhalation. The primary objective of the study was to assess the pulmonary deposition of BGF. Secondary objectives assessed the deposited dose of radiolabeled BGF in the oropharyngeal and stomach regions, on the actuator, and on the exhalation filter in addition to regional airway deposition patterns in the lungs. Results The mean BGF emitted dose deposited in the lungs was 32.1% (standard deviation [SD] 15.6) in patients with moderate-to-very severe COPD, 35.2% (SD 12.8) in patients with moderate COPD, and 28.7% (SD 18.4) in patients with severe/very severe COPD. Overall, the mean normalized outer/inner ratio was 0.55 (SD 0.19), while the standardized central/peripheral ratio was 2.21 (SD 1.64). Conclusions Radiolabeled BGF 320/18/9.6 μg was efficiently delivered and deposited throughout the entire lung, including large and small airways, in patients with moderate-to-very severe COPD, with similar deposition in patients with moderate COPD and patients with severe/very severe COPD. Trial registration: ClinicalTrials.gov, NCT03906045. Registered 8 April 2019, https://clinicaltrials.gov/ct2/show/NCT03906045

Budesonide-Glycopyrronium-Formoterol Fumarate Dihydrate (Breztri Aerosphere)

CADTH recommends that Breztri Aerosphere be reimbursed by public drug plans for the treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema if certain conditions are met. Breztri Aerosphere should only be covered to treat patients who are not controlled on optimal dual inhaled therapy for COPD. Breztri Aerosphere should be reimbursed similar to Trelegy Ellipta. The price of Breztri Aerosphere should not exceed the drug program cost with the least-costly fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist/long-acting beta2-agonist (ICS/LAMA/LABA) triple therapy combination for the same indication.

EPOC: Enfoque personalizado para el tratamiento según la guía GOLD 2021

<b>Background:</b> In the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied. <b>Methods:</b> KRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported. <b>Results:</b> Of 1896 patients analyzed, 948 (50%) were non-reversible and had EOS &#x3c;300 cells/mm³. In this group, BGF significantly improved morning pre-dose trough FEV₁ versus BFF and BUD/FORM (least squares mean treatment difference, 95% confidence interval [CI] 69 mL [39, 99], unadjusted <i>p</i> &#x3c; 0.0001 and 51 mL [20, 81], unadjusted <i>p</i> = 0.0011, respectively) and was comparable to GFF. BGF also significantly reduced annual moderate-to-severe exacerbation rates versus GFF (rate ratio [95% CI] 0.53 [0.37, 0.76], unadjusted <i>p</i> = 0.0005), with numerical reductions observed versus BFF and BUD/FORM. These results were similar for the overall study population. Safety findings were generally similar between non-reversible patients with EOS &#x3c;300 cells/mm³ and the overall population. <b>Conclusions:</b> In patients with moderate-to-very-severe COPD without airway reversibility and EOS &#x3c;300 cells/mm³, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM and significantly reduced the rate of moderate-to-severe exacerbations versus GFF. These findings demonstrate that BGF can provide benefits for a broad range of patients with COPD, and that the overall findings of the KRONOS primary analysis were not driven by patients with reversible airflow obstruction or high eosinophil counts. <b>Trial registration:</b> ClinicalTrials.gov, NCT02497001. Registered 14 July 2015, https://clinicaltrials.gov/ct2/show/NCT02497001

Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive Pulmonary Disease

Objective: To review current evidence on the use of a fixed-dose combination (FDC) of budesonide/glycopyrrolate/formoterol fumarate (BGFF) triple therapy delivered via metered dose inhaler (MDI) in patients with chronic obstructive pulmonary disease (COPD) and offer clinical practice insights. Data Sources: We used PubMed to conduct the literature search from 1946 through June 30, 2021, using budesonide, glycopyrrolate or glycopyrronium, and formoterol. Study Selection and Extraction: We included clinical trials in patients with COPD along with pharmacokinetic or pharmacodynamic studies. Data Synthesis: In all, 19 citations were included. BGFF MDI reduces the risk of exacerbations regardless of exacerbation history compared with dual bronchodilators or inhaled corticosteroid/long-acting β-agonist. Rescue inhaler use decreased, and patient-reported outcomes of symptoms and well-being improved with triple therapy. Mortality was decreased with the higher-dose BGFF MDI in comparison to dual bronchodilator therapy. Dysphonia and candidiasis were more common with BGFF MDI compared with dual bronchodilators, as was pneumonia. Relevance to Patient Care and Clinical Practice: BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia. Conclusion: The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.

Validation of Novel Analytical RP-HPLC Method for determination of Formoterol Fumarate and Budesonide in Inhalation Suspension Pharmaceutical Dosage Form

Formoterol Fumarate and Budesonide inhalation suspension is prescribed for treatment of Asthmatic patient. Formoterol Fumarate is anti-asthmatic drug (Bronchodilator) and Budesonide is Anti Inflammatory Drug (Glucocortico steroid) drug. A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs while Anti Inflammatory drug is used for the treatment of inflammation occurred on respiratory tract. The present study aimed to Validate HPLC method for combined determination of Assay of Formoterol Fumarate and Budesonide Analytes. This study covers Precision, Limit of Detection, Limit of Quantification, Linearity, Accuracy, Robustness, Ruggedness, Solution stability and Specificity. The chromatographic method uses a reversed phase column Hypersil ODS 125mm ×4.0mm x 5μm). The mobile phase was prepared by mixing Acetonitrile: Phosphate buffer (35:65, %v/v) at flow rate 1.0ml/min with Ultraviolet and Diode array detector at wavelength 215nm, column oven adjusted to 40°C and with injection volume 50μL. The method Found Precise, Accurate, Linear, Rugged, Robust and Sensitive. The method showed a successful application for determination of Formoterol Fumarate and Budesonide in Inhalation suspension pharmaceutical formulation.