Tozorakimab Scores Double Win in Phase III COPD Trials

AstraZeneca has scored a “double win” for its obstructive pulmonary disease (COPD) biologic therapy, tozorakimab, in two Phase III trials.

The first-in-class therapy delivered positive topline data in the Phase III Oberon and Titania trials, meeting primary endpoints in both.

Related: Boehringer’s Jascayd Scores Second FDA Approval in Lung Fibrosis

COPD remains one of the leading causes of death worldwide, driven primarily by smoking and environmental exposures, and characterized by progressive airflow limitation punctuated by exacerbations. Worldwide, almost 400 million people are diagnosed with COPD, and the condition is the third leading cause of death globally. 

According to information from AstraZeneca in its press release, despite receiving inhaled standard of care, more than 50% of patients experience exacerbations, which leads to an increased risk of cardiopulmonary events and mortality.

And despite its global burden, drug development in COPD has historically lagged behind other respiratory conditions like asthma.

In the two late-stage trials, tozorakimab met its primary endpoint: significant reduction of the annual rate of moderate-to-severe exacerbations compared to placebo. The main population cohort in the studies was comprised of former smokers.

But the efficacy signal was consistent across a broader population of both current and former smokers, patients with varying lung function and those with different inflammatory profiles.

Tozorakimab is a monoclonal antibody that targets interleukin-33 (IL-33), an upstream inflammatory mediator implicated in airway inflammation and mucus dysfunction. The therapy blocks both reduced and oxidized forms of IL-33, potentially enhancing its biological impact.

Additionally, AstraZeneca has asserted that tozorakimab is a differentiated asset compared to competitors itepekimab (Sanofi and Regeneron) and astegolimab (Roche/Genentech), as it fully inhibits the ST2 and RAGE/EGFR signaling cascades. The company explains that RAGE/EGFR affects mucus production, which leads to epithelial remodeling that decreases lung function in COPD patients and also drives exacerbations.

AstraZeneca has emerged as the first IL-33 player to demonstrate consistent efficacy. In contrast, Sanofi and Regeneron reported one success and one failure in their Phase III itepekimab program. Roche had a Phase IIb win with astegolimab, which it licensed from Amgen, but disappointing results in a Phase III study.

But differences in trial design could explain AstraZeneca’s triumph over the mixed trial results of its competitors. According to reporting by Fierce Pharma, TD Cowen analysts noted that Roche’s astegolimab showed greater benefit in patients with more frequent exacerbations. However, AstraZeneca’s larger trials, conducted closer to the end of COVID-19 lockdowns, likely captured higher exacerbation rates overall, registering as a win overall.

“Today’s tozorakimab results deliver the first two confirmatory Phase III trials for an IL-33 biologic, which is a major scientific advancement in COPD, the world’s third leading cause of death. Tozorakimab works in a fundamentally different way from other biologics, inhibiting the signaling of the reduced and oxidized forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction that are key disease drivers in COPD,” Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said in a company announcement.

Detailed results from the trials are expected at an upcoming medical conference.

The latest results bolster AstraZeneca’s confidence in tozorakimab, as it previously said the asset could deliver peak sales of $3 billion to $5 billion. 

Investor confidence also appeared to mirror AstraZeneca’s. Company shares rose quickly following the announcement of the latest study data.