The FDA approved budesonide/glycopyrrolate/formoterol fumarate (Breztri Aerosphere) in a single inhaler as maintenance therapy for asthma in adults and children 12 years and up, AstraZeneca announced on Tuesday.
Approval of the corticosteroid, long-acting beta-agonist (LABA), and long-acting muscarinic antagonist triple inhaler was supported by the phase III KALOS and LOGOS trials, which in a broad population demonstrated improvements in lung function paired with a drop in severe exacerbations versus a budesonide/formoterol fumarate (Symbicort) metered-dose inhaler.
“Despite the availability of dual maintenance therapy, many patients are still at risk for exacerbations and experience daily breathing difficulties, reduced lung function, and the ongoing fear of worsening symptoms,” investigator Njira Lugogo, MD, of the University of Michigan in Ann Arbor, said in a statement. “The FDA approval of Breztri as the only maintenance triple therapy for people with asthma 12 years of age and older marks a pivotal moment in helping those living with this debilitating disease breathe better, sooner.”
The studies together included more than 4,300 patients 12 years and up and included those with or without a recent asthma exacerbation.
At the approved dose (320/36/9.6 μg twice daily), the change from baseline to 24 weeks in morning pre-dose trough forced vital capacity in 1 second (FEV1) — the primary endpoint in the two trials — was reduced by 71-91 mL with the triple therapy maintenance compared with dual therapy (P<0.001).
Annualized severe exacerbations with the triple therapy declined by 18% to 20%. Common adverse events included nasopharyngitis, pneumonia, and headache.
The triple therapy first gained approval for chronic obstructive pulmonary disease in 2020. In asthma, it joins fluticasone furoate/umeclidinium/vilanterol (Trelegy Ellipta), a triple therapy approved for adults 18 and over.
As per the new asthma indication, budesonide/glycopyrrolate/formoterol fumarate is contraindicated for status asthmaticus or other acute asthma events.
A lengthy warnings and precautions section in the drug labeling includes notes about the risk for overdose if taken at higher doses or if combined with other LABA-containing products, oropharyngeal candidiasis, lower respiratory tract or other serious infections, hypersensitivity reactions including anaphylaxis, hypercorticism and adrenal suppression, hypokalemia or hyperglycemia, worsening of urinary retention, glaucoma and cataracts, and decreases in bone mineral density.
For patients on systemic corticosteroids, a slow tapering is required before transferring to the inhaled corticosteroid-containing product, as deaths due to adrenal insufficiency have been reported with acute transfers.
Caution is required in patients with certain cardiovascular disorders or hepatic impairment and those on monoamine oxidase inhibitors, tricyclic antidepressants, or long-term ketoconazole and other strong CYP3A4 inhibitors.
Other drug interactions are also possible, including with strong cytochrome P450 3A4 inhibitors, adrenergic drugs, xanthine derivatives, steroids, non-potassium sparing diuretics, beta-blockers, and anticholinergic-containing drugs.
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