November 14, 2022
3 thousand trains
Chipps B, et al. Abstract D015. Presented at: ACAAI Annual Scientific Meeting; Nov. 10-14, 2022; Louisville, Ky.
Chipps reports that he has served as a consultant/speaker for and received consulting fees from AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron, and Sanofi Genzyme. He also serves as a consultant to Bond Avillion 2 Development, which funded this study.
LOUISVILLE, Ky. — Patients who received albuterol and budesonide experienced fewer exacerbations and worsening of asthma over 12 weeks compared with patients who received monotherapy or placebo, according to the results of the DENALI study.
These findings were presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
“When asthma symptoms worsen, patients typically rely on short-acting beta-blockers as rescue therapy; however, short-acting rescue therapy provides rapid relief from bronchospasm, but does not address the inflammatory component of the airways that drives worsening airway symptoms. Bradley E. Chippsdoctor, director of respiratory therapy and cystic fibrosis at Sutter Medical Center, said during his presentation. “There is a window of opportunity that can be interrupted, stop the progression of inflammation and prevent progression, by treating symptoms and inflammation concurrently.”
Thus, Chipps and colleagues conducted the phase 3, randomized, 12-week, double-blind, multicenter DENALI trial to evaluate fixed-dose albuterol and budesonide in a single-dose inhaler (PT027, Avillion).
As previously reported by Healio, the primary analysis of DENALI showed a significant benefit in patients with asthma when they received a fixed-dose combination of albuterol and budesonide 180/160 µg and 180/80 µg, confirming that both monocomponents contributed to lung function. action of albuterol-budesonide.
In an exploratory analysis of the study, Chipps and colleagues evaluated data on 989 patients, 12 years of age or older, with mild to moderate asthma to see how albuterol-budesonide worked against each of its individual components and placebo for asthma exacerbations and severe asthma. asthma exacerbation, according to the abstract of the study.
Researchers randomly assigned 197 patients (mean age, 50 years; 63.5% female) to albuterol-budesonide 180/160 µg, 201 patients (mean age, 49.2 years; 63.2% female) to albuterol- budesonide 180/80 µg patients. (mean age 47.8 years; 60.7% female) to albuterol 180 µg, 199 patients (mean age 48.3 years; 60.3% female) to budesonide 160 µg and 196 patients (mean age 49.2 years; 63.3 % women) in placebo. Each drug was administered four times daily for 12 weeks, in addition to albuterol sulfate inhaler (Ventolin HFA, GSK) required for asthma symptoms.
“While four-times-daily dosing does not reflect the intended real-life use of albuterol-budesonide on an as-needed basis, the DENALI study design required scheduled dosing to assess the contribution of both the budesonide and albuterol monocomponents to the efficacy of this fixed-drug combination,” Chipps said. “Four-times-daily dosing also provided the opportunity to assess the safety of regular use over 12 weeks … at significantly higher doses than expected for as-needed dosing.”
At 12 weeks, fewer patients receiving both albuterol-budesonide 180/160 µg (34.5%) and 180/80 µg (42.3%) had one or more asthma exacerbations compared to the other treatment groups (albuterol, 58.7% ; 47.7, %; placebo, 53.6%).
“The total number of asthma exacerbations was approximately twice as low in the high-dose albuterol-budesonide group [at 154] than in the albuterol group [at 320]Chips said. “A similar trend was seen with the average number of asthma exacerbations per patient and the proportion of patients with at least one asthma exacerbation.”
Researchers also found that fewer patients receiving either treatment dose of albuterol budesonide had at least one serious exacerbation during the 12-week treatment period than patients receiving albuterol or placebo (albuterol budesonide 180/160 µg, 2%; 180/80 µg, 2, 5%, albuterol, 10.2%, placebo, 7.1%). The researchers also saw fewer serious exacerbations among patients who received budesonide alone (2%).
In addition, patients treated with albuterol-budesonide 180/160 µg and 180/80 µg had only 22 and 31 days of progression, respectively, compared to those treated with albuterol 130 days, budesonide 42 days, and placebo 85 days with progression, according to progression. abstract.
“DENALI confirmed the contribution of both monocomponents to the lung function of the fixed-dose combination,” Chipps said, adding that the drug is being developed for use as needed, not four times a day.