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

After AstraZeneca’s fast-growing respiratory biologic Fasenra failed to move the needle in a COPD trial, hopes were directed to its three-in-one inhaler Breztri. But the potential challenger to GlaxoSmithKline’s Trelegy will have to wait a little longer—if not forever—in the U.S.

The FDA has declined to approve Breztri Aerosphere, also known as PT010, for COPD, AstraZeneca said Tuesday.

There’s no word on the exact nature of the complete response letter, but AZ did say it will submit results from another phase 3 trial, which only came off recently and were not included in its original new drug application package.

Meanwhile, the drug has already picked up its first global approval, from Japanese authorities in June. It’s also under priority review in China, and the EMA is assessing its application, too.

AZ first reported that the phase 3 Kronos study turned out positive early last year. Then in a detailed update last September, the British drugmaker said the triplet had met eight of nine primary endpoints in the head-to-head against its two-drug combos Bevespi Aerosphere, old stalwart Symbicort and its lower-dosed version using the Aerosphere delivery technology, PT009.

The only miss was in its ability to reduce the rate of sudden worsening of COPD symptoms, in which it delivered only a numerical advantage over either Symbicort or PT009, rather than one that was statistically significant.

RELATED: AstraZeneca's Breztri scores in COPD trial, amping its case for triple-combo battle against GSK

But in August, AZ said data from the phase 3 Ethos trial showed Breztri could significantly reduce the rate of exacerbations compared with the other two Aerosphere-delivered dual-drug combos, Bevespi and PT009, at both the standard budesonide dose and at half the amount of the steroid. Bevespi and PT009 each comprise two of the three drugs used in Breztri.

Because data showed benefit at two corticosteroid doses, the study’s lead investigator, Klaus Rabe, argued it “could transform treatment practice by allowing physicians to select the optimal dose for individual patients.”

The company has yet to unveil detailed numbers from that study.

The Breztri FDA setback comes not long after AZ’s COPD hopes for biologic growth driver Fasenra were dashed on the back of two disappointing phase 3 studies.

Now, AZ’s ambitions to hang with GSK in the triple combo arena are on hold as well, giving its rival’s Trelegy Ellipta a longer launch runway all to itself and possibly a firmer market foothold. In the second quarter, Trelegy contributed £120 million ($147 million) to GSK’s top line.

The GSK drug recently posted a mixed phase 3 trial performance in asthma. In the Captain study, Trelegy beat GSK’s own Breo Ellipta at improving lung function after 24 weeks in those with uncontrollable asthma, meeting the trial’s primary endpoint. But just as Breztri previously struggled with COPD exacerbations, Trelegy also failed to show significant benefits when it came to a reduction in asthma aggravations.