The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Wixela Inhub: A Generic Equivalent Treatment Option for Patients with Asthma or COPD.

PURPOSE: The purpose of this review is to discuss the development of Wixela™ Inhub™, a generic equivalent of Advair Diskus®, a fixed-dose combination of fluticasone propionate/salmeterol powder for oral inhalation for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide an overview of the Inhub device and the bioequivalence studies that have been conducted to date. Briefly, the in vitro performance, improvements in forced expiratory volume in 1 s, and the fluticasone propionate/salmeterol dose strengths for Wixela Inhub and Advair Diskus were comparable. CONCLUSION: The bioequivalence demonstrated by the totality of clinical and in vitro data supports the use of Wixela Inhub and provides a treatment option for patients with asthma or COPD.

The Wixela™ Inhub™ device has been developed as a generic equivalent of Advair Diskus^®, and provides a combination treatment for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide information about the Inhub device and studies conducted to show how Inhub and Diskus are comparable products. Based on the similar results between the two devices, Inhub can be used as a treatment option for patients with asthma or COPD.

Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma.

Background: Wixela® Inhub® is a dry powder inhaler approved as a generic equivalent to Advair® Diskus® (fluticasone propionate [FP]/salmeterol fixed-dose combination) for patients with asthma or chronic obstructive pulmonary disease (COPD). This study aimed at confirming the local (lung) therapeutic equivalence of both the FP and salmeterol components of Wixela Inhub (test [T]) to Advair Diskus (reference [R]) after inhalation. Methods: This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study in patients ≥18 years with mild-to-moderate persistent asthma compared the local therapeutic equivalence (using forced expiratory volume in 1 second [FEV1]) of FP/salmeterol (100/50 µg) after inhaled delivery via T and R. Results: Randomized patients (N = 1127) received T (n = 512), R (n = 512), or placebo (n = 103). T and R significantly increased day 1 FEV1 area under the effect curve over 12 hours of the change from baseline (AUC[0-12]) and day 29 trough FEV1 over placebo, indicating that these endpoints were sufficiently sensitive for evaluation of bioequivalence. On day 1, T and R each increased FEV1 AUC(0-12) over placebo (3.134 L•h [T], 2.677 L•h [R]; each p < 0.0001). Following twice-daily dosing for 28 days, T and R also each increased trough FEV1 (measured on day 29) over placebo (235 mL [T], 215 mL [R]; each p < 0.0001). Least-squares mean T/R ratios (90% confidence intervals) for day 1 FEV1 AUC(0-12) and day 29 trough FEV1 were 1.120 (1.016-1.237) and 1.069 (0.938-1.220), respectively, indicating that T and R were bioequivalent for both co-primary endpoints. FP/salmeterol was well tolerated when administered via either T or R. Conclusions: These results demonstrate that the therapeutic effects of Wixela Inhub are bioequivalent to Advair Diskus in the lung. Wixela Inhub represents a therapeutically equivalent new FP/salmeterol treatment option for use in the treatment of asthma and COPD.

Long-term safety and efficacy of formoterol fumarate inhalation solution in patients with moderate-to-severe COPD.

BACKGROUND: Formoterol fumarate inhalation solution (FFIS; Perforomist®) is a long-acting ß2-agonist (LABA) marketed in the US as a nebulized COPD maintenance treatment. Because long-term LABA use was associated with a potential increased risk of exacerbation or death in asthma patients, the US Food and Drug Administration (FDA) requested a postmarketing commitment study to evaluate long-term safety in COPD patients. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, noninferiority study. Patients (N=1,071; mean age, 62.6 years; 48.5% male; 89.7% white) with moderate-to-severe COPD on stable COPD therapy received FFIS (20 µg; n=541) or placebo (n=530) twice daily. The primary end point was the combined incidence of respiratory death, first COPD-related ER visit, or first COPD exacerbation-related hospitalization during 1 year post randomization. Noninferiority to placebo was concluded if the two-sided 90% CI of the HR of FFIS to placebo was <1.5. Secondary end points included spirometry. RESULTS: The planned 1-year treatment period was completed by 520 patients; 551 discontinued prematurely (FFIS: 45.7%; placebo: 57.4%). The median treatment duration was approximately 10 and 7 months for FFIS and placebo, respectively. Among 1,071 randomized patients, 121 had ≥1 primary event (FFIS: 11.8%; placebo: 10.8%). The estimated HR of a primary event with FFIS vs placebo was 0.965 (90% CI: 0.711, 1.308), demonstrating that FFIS was noninferior to placebo. No respiratory deaths were observed in the FFIS group. Adverse events were similar for FFIS vs placebo (patients with ≥1 treatment-emergent adverse events: 374 [69.1%] vs 369 [69.6%], respectively). Compared with placebo, FFIS demonstrated statistically greater improvements from baseline in trough FEV1, FVC, percent predicted FEV1, and patient-reported outcomes (Transition Dyspnea Index). CONCLUSIONS: Nebulized FFIS was noninferior to placebo with respect to safety in patients with moderate-to-severe COPD. Additionally, fewer treatment withdrawals and larger lung function improvements were observed with FFIS compared with placebo when added to other maintenance COPD therapies.