Source / Disclosures
Papi A et al. The New England Journal of Medicine And gamma Discussion on the Edge: Recently Published Pulmonary Research Reports. Presented at: International Conference of the American Thoracic Society. May 13-18, 2022; San Francisco (mixed meeting).
Chips reported on consulting for AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Regeneron and Sanofi. Papi reports receiving grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, and Sanofi/Regeneron; Personal drawings from Edmund Varma, Mandi Varma, Novartis, Roche and Zamboon; Grants from Fondazione Maugeri and Fondazione Chiesi; and advise Bond Avillion 2 Development LP.
SAN FRANCISCO – In patients with moderate to severe uncontrolled asthma, fixed-dose albuterol and budesonide as rescue medication as needed reduces the risk of severe asthma exacerbations compared to albuterol alone.
“MANDALA achieved the primary end point: budesonide albuterol significantly reduced the risk of exacerbations versus albuterol,” Alberto Pape, MD, Professor of Respiratory Medicine at the University of Ferrara Medical School in Italy, said during a presentation of the findings at the International Conference of the American Thoracic Society. The results were simultaneously published in The New English Journal of Medicine.
In the pre-planned efficacy analysis, the primary end point for first acute asthma exacerbation was 27% lower among patients assigned a fixed-dose albuterol 180 mcg and budesonide 160 mcg compared to albuterol 180 mcg alone (HR = 0.73; 95% CI, 0.61–0.88; s < .001) and 17% lower with the lower-dose combination of albuterol 180 mcg and budesonide 80 mcg (heart rate = 0.83; 95% confidence interval, 0.7–0.99; q = .041). In the intent-to-treat analysis, risk was reduced by 26% with the higher dose combination (HR = 0.74; 95% CI, 0.62–0.89; q = .001) and 16% with the lower-dose combination (heart rate = 0.84; 95% confidence interval, 0.71-1; q = .052),” Babi said during the show.
The study treatment, PT027, is a potential Class I inhaled fixed-dose salvage drug containing short-acting beta-2 albuterol and the inhaled corticosteroid budesonide in the United States. Company press release.
The fixed-dose inhaler was developed to provide rapid relief of asthma symptoms and simultaneously treat fluctuation in primary inflammation when needed, according to Pappe.
“Albuterol by itself, although it initially works with good bronchodilation, does not affect the inflammatory component of asthma and as a result does not prevent exacerbation of the disease. We know that a third to 45% of patients with mild asthma have an exacerbation each year. We need to intervene. In a “window of opportunity,” that is, when asthma control is lessened as people become more likely to prevent its progression to an exacerbation, “ Bradley E. Shepps, MD, The former president of the American College of Allergy, Asthma, and Immunology and medical director of the Capital Center for Allergy and Respiratory Diseases in Sacramento, California, told Healio. The message this trial will take home is: “You can prevent your patients from having to take oral corticosteroids. Regardless of what you think your patients are doing, many don’t take their medication; they view asthma as an occasional illness. These [fixed-dose combination rescue inhaler] It helps stop episodic increases in symptoms before they develop into an exacerbation,” said Chips.
The third, double-blind, randomized, event-driven phase included symptomatic patients aged 4 years and older who had moderate to severe asthma and at least one severe exacerbation in the previous year. The median age was about 49 years, two-thirds of whom were female and 81% were white. A total of 3132 patients were randomly assigned to the high-dose group, the low-dose group, or albuterol only; Of these, only 183 ranged in age from 4 to under 18. The study drug was administered via a pressurized metered-dose inhaler in two procedures. All patients were receiving maintenance inhaled corticosteroids alone or in combination with other control medications.
The fixed-dose combination also reduced mean annual total systemic corticosteroid exposure and annual acute exacerbation rate, according to NEJM Publishing. The researchers reported numerically higher odds of improvement in symptom control and quality of life with the fixed-dose combination.
The incidence of any adverse event was similar across the three groups, at 46.2% in the high-dose combination group, 47.1% in the low-dose group and 46.4% in the albuterol-only group. Serious adverse events occurred in 5.2%, 3.8% and 4.5%, respectively. Adverse events were consistent with the known safety profiles of the individual components; The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection.
“Given the efficacy of adding budesonide to albuterol as a rescue drug and the duration of treatment, we believe this would be a potential paradigm change for the use of rescue drugs,” Papy said.
Three phase III studies evaluating a fixed-dose combination of albuterol budesonide as a meter-dose pressurized inhaler in asthmatic patients have now been completed: TYREE, MANDALA and DENALI. DENALI will be presented later during the ATS International Conference; This article will be updated.