FDA clears Breztri for asthma and adds a lower-warming propellant

The Food and Drug Administration approved a new formulation of Breztri Aerosphere on 8 October, and with it a second use: the maintenance treatment of asthma in patients aged 12 and older [s1][s2]. The inhaler, made by AstraZeneca, was already cleared for chronic obstructive pulmonary disease; the asthma indication is the addition [s1].

Breztri is a triple therapy. Each puff delivers an inhaled corticosteroid (budesonide), a long-acting muscarinic antagonist (glycopyrrolate) and a long-acting beta-agonist (formoterol) [s1]. The asthma label is specific: it is for maintenance, not rescue, and the prescribing information states plainly that Breztri is not indicated for the relief of acute bronchospasm [s1].

The second change: the propellant

This approval also carries an environmental footnote that is unusual for a drug docket. The application, cleared under the 505(b)(2) pathway, is for Breztri containing a new propellant, HFO-1234ze(E), in place of the older hydrofluoroalkane HFA-134a [s2]. Pressurised metered-dose inhalers release their propellant into the air with every actuation, and HFA-134a is a potent greenhouse gas; HFO-1234ze(E) has a far lower global-warming potential. The label lists both propellant versions, so the lower-warming formulation enters a market where the older one still exists [s1].

What the asthma trials showed

The asthma indication rests on two identically designed, randomised, double-blind trials, KALOS (NCT04609878) and LOGOS (NCT04609904), of 24 to 52 weeks [s1]. They enrolled adults and adolescents 12 and older whose asthma stayed inadequately controlled — an Asthma Control Questionnaire-7 score of at least 1.5 — despite a medium or high dose of an inhaled corticosteroid plus a long-acting beta-agonist [s1]. The efficacy comparison was Breztri 320/36/9.6 mcg against a two-drug inhaler, budesonide/formoterol (BFF) 320/9.6 mcg; the efficacy populations were 1,200 subjects in KALOS and 1,187 in LOGOS [s1]. The contrast is therefore triple therapy against dual: the extra ingredient being tested is glycopyrrolate.

The primary endpoint was the change from baseline in lung function — FEV1 area under the curve over the first three hours after dosing — at Week 24 [s1]. Breztri won on this measure in both trials. The adjusted mean improvement was 316 mL on Breztri versus 249 mL on BFF in KALOS, a difference of 68 mL (95% CI 29 to 106), and 354 versus 219 mL in LOGOS, a difference of 134 mL (95% CI 93 to 175) [s1]. Trough FEV1, the key secondary measure, moved in the same direction, with between-group differences of 42 mL in KALOS and 107 mL in LOGOS, both statistically significant [s1].

Where the drug did not clearly separate is the outcome patients care about most. In the pooled analysis, the annualised rate of severe asthma exacerbations was 0.54 on Breztri and 0.60 on BFF — a rate ratio of 0.90, with a 95% confidence interval of 0.78 to 1.03 that crosses 1 [s1]. Asthma control, measured by ACQ-7 responder rates, was also similar between the two inhalers at Week 24 [s1]. So the established benefit is on spirometry, not on flare-ups or symptom control, against an active two-drug comparator.

Safety, briefly

In the pooled asthma safety population of 1,179 subjects on Breztri, the adverse reactions reported at 2% or more, and more often than on BFF, were nasopharyngitis (9.4%), pneumonia (2.8% versus 2.2%) and headache (2.2%) [s1]. Pneumonia is a recognised risk of inhaled corticosteroids. As a class, long-acting beta-agonists carry a history of concern about asthma-related events, and the label reflects the standard framing that an ICS/LABA combination should not show a meaningful increase in serious asthma-related events compared with the corticosteroid alone [s1].

What to watch

Two things. First, whether the lung-function advantage of adding a LAMA translates, outside a trial, into fewer attacks for people whose asthma is already on two controllers — the trials did not demonstrate that. Second, whether the lower-warming propellant displaces the older formulation in practice, since the climate benefit of the switch only materialises if prescribers and payers move to it.

Red flags for anyone with asthma: Breztri is a daily controller, not a reliever. Needing a rescue inhaler more often, waking at night breathless, or a peak-flow drop are signs of worsening control that warrant prompt medical review, not a higher dose taken alone. Sudden severe breathlessness is an emergency.

This article describes an FDA approval and its labelling and is not medical advice. Decisions about asthma or COPD treatment belong with a clinician who knows the individual case.