AstraZeneca touts triplet inhaler Breztri's COPD win ahead of key FDA decision

AstraZeneca, hoping to win over the FDA on a second try, showed that its COPD triplet Breztri Aerosphere led to a 24% reduction in exacerbations compared with its dual drug regimen Bevespi Aerosphere. (AstraZeneca)

The future of AstraZeneca’s three-in-one inhaler Breztri, which was previously hit with a surprising FDA rejection, was hinging on the outcome of another phase 3 trial. And the results from that trial look good.

Detailed data published in The New England Journal of Medicine showed Breztri significantly cut the rate of exacerbations compared with two dual-drug combo therapies in patients with moderate to severe COPD.

AstraZeneca has already shared the data with the FDA, which didn’t see them in the original application package. The company expects a ruling later this year, Ruud Dobber, AZ’s biopharma president, told investors during a conference call in April.

According to results from the large-scale Ethos trial, treatment with Breztri Aerosphere reduced exacerbations over 52 weeks by 24% compared with AZ's Bevespi Aerosphere and 13% compared with PT009, a candidate that contains the same ingredients as aged blockbuster Symbicort. Breztri did that at both the standard 320μg budesonide dose and at half that strength.

Specifically, 2,137 patients on the 320-μg budesonide version of Breztri experienced 1.08 COPD exacerbations per year. The annual rate was even marginally better for 2,121 patients on the 160-μg regimen, at 1.07. In comparison, the rates for Bevespi and PT009 were 1.42 and 1.24, respectively.

What’s more, standard Breztri also showed a favorable, numerical trend against Bevespi in lowering the risk of all-cause death. That improvement means that “reducing risk of all-cause mortality is achievable and could transform treatment goals in chronic obstructive pulmonary disease,” Klaus Rabe, lead investigator of the Ethos trial, said in a statement.

RELATED: FDA stonewalls AstraZeneca's COPD triplet Breztri, handing GSK's Trelegy a reprieve

Previously in the phase 3 Kronos trial, which had nine primary endpoints, the three-in-one inhaler missed one that pitted it against Bevespi on flare-ups at week 24.

Breztri is already approved in Japan and China. But the FDA rejection last fall gave rival GlaxoSmithKline a longer runway in the U.S. triplet market with its 2017-approved Trelegy Ellipta. Last year, the GSK three-drug regimen raked in sales of £518 million ($643 million).

The two British drugmakers have long been at each other’s throats in the respiratory market. Elsewhere in the field, AZ’s asthma biologic Fasenra is competing against GSK’s Nucala.

At first glance, Trelegy’s performance in its own clinical trial appears to be better than Breztri’s, although researchers consider cross-trial comparisons problematic. In the Impact study comparing Trelegy to fixed-dose double-therapy options administered via GSK’s Ellipta inhaler, patients on the triple therapy reported a rate of 0.91 moderate to severe exacerbations per year.