GlaxoSmithKline has seized the initiative with its three-drug COPD inhaler Trelegy Ellipta despite some new competition from AstraZeneca. To cement its lead, GSK is looking for a first-of-its-kind label update showing Trelegy could cut patients' risk of death—but does the data actually support it?
An FDA advisory committee will decide today whether to recommend adding all-cause mortality data to Trelegy's label, based on follow-up findings from the pivotal study used to secure the drug's COPD approval in 2017.
That trial, dubbed Impact, showed the triple-drug combo cut the risk of death during and after treatment by 27.7% over Anoro Ellipta, a GSK combo that contains just two of Trelegy's three drugs. A green light would make Trelegy the first COPD med with such language on its label.
However, Cowen & Co. analysts called GSK's chances at a label expansion a "long shot" based on uncertainty whether the trial's design "artificially inflated" Trelegy's relative benefits.
Patients in both arms of the Trelegy versus Anoro portion of the study were treated with an inhaler at the time of randomization and then rapidly taken off during the trial. That design could have resulted in an observed early spike in disease exacerbations and deaths in the Anoro arm, Cowen said.
Cowen's consultants, moreover, said adding mortality data to Trelegy's label was a bit of an unnecessary endeavor given COPD medications' traditional role in easing symptoms rather than extending lives. Trelegy has already proven itself there—and therefore a label update wouldn't do much to boost Trelegy's uptake, the analysts figure.
"The primary goal of pharmacological treatment is to ameliorate symptoms of COPD and to prevent exacerbations," they wrote in a note to clients last week. "Trelegy has already demonstrated an impressive profile on the factors driving the choice of triple therapy; therefore our consultants already consider it the agent of choice and advocate its use to their colleagues in the community."
In a statement, GSK admitted the bar for a label expansion was high but worth the effort.
"We knew in making the application to the regulatory authorities this was a high bar to achieve, but we felt it was important to make the submission in order to have the scientific discussion about this potential label update," the company said.
Indeed, Trelegy has raced to a lead as the leading triple-drug combo in COPD. Glaxo is looking to preserve that lead as British rival AstraZeneca works to boost its own candidate in the field.
In July, the FDA approved AstraZeneca’s three-in-one Breztri Aerosphere for the maintenance treatment of COPD. The drug is a combination of the three ingredients included in AZ’s two dual-drug regimens Symbicort and Bevespi.
AZ's Breztri approval came more than a year after the FDA leveled the drug with a complete response letter. The drug missed one of its nine primary endpoints in the pivotal phase 3 study for that regulatory filing, but AstraZeneca later submitted data from another phase 3 study that helped get the therapy across the finish line.