Roche's COPD candidate fails a phase 3 readout

Roche has posted a mixed set of data from two clinical trials of its anti-IL-33/ST2 antibody astegolimab in chronic obstructive pulmonary disease (COPD), casting a shadow over the programme.

On the plus side, astegolimab met its main objective in the phase 2b ALIENTO study, achieving a statistically significant 15.4% reduction in the annualised exacerbation rate (AER) – the flare-ups in symptoms that signal progression of the disease – compared to placebo at one year.

The outcome of the phase 3 ARNASA trial was less positive, however, with a 14.5% reduction in AER compared to control at the same time point, which did not pass the significance threshold.

The two studies were of similar size, each with more than 1,300 patients, and tested astegolimab given once every two weeks. They included a broad, 'all-comer' population of COPD patients, including former and current smokers, as well as those with a wide range of blood eosinophil counts.

That could be significant, as recent approvals for biologic therapies in COPD – including Sanofi/Regeneron's IL-4 and IL-13 inhibitor Dupixent (dupilumab) and GSK's IL-5 inhibitor Nucala (mepolizumab) – are both approved to treat patients with high levels of eosinophils.

The design of ARNASA and ALIENTO set a higher bar for astegolimab to clear, but its top-line reduction in AER of around 15% undershoots the readouts from pivotal trials of Dupixent and Nucala, which cut the rate by around a third and 21%, respectively, in their narrower patient populations.

Roche said there was a lower-than-expected rate of AERs in both studies, which would have made it harder to show a significant improvement, pointing out that the effect of the drug on secondary measures – which included time to first moderate or severe COPD exacerbation, lung function scores, and patient-reported outcomes – was "generally consistent," although it did not provide further details.

The ALIENTO and ARNASA results will be discussed with regulatory authorities and shared at an upcoming medical meeting, said the company in a statement.

"While COPD remains the third leading cause of death worldwide, patients and families have limited treatment options for managing this debilitating and complex disease," said Levi Garraway, Roche's chief medical officer.

"This was the first set of studies in an 'all-comers' COPD population, and we will discuss these data with regulatory authorities to evaluate next steps for astegolimab," he added.

COPD is the third leading cause of death worldwide and affects more than 300 million people globally.