Where others missed, AZ's IL-33 drug hits the mark in COPD

AstraZeneca's IL-33-targeting antibody tozorakimab has made the grade in two phase 3 chronic obstructive pulmonary disease (COPD) trials, raising the prospects of a class that has recorded some notable failures in the past.

Top-line results from the OBERON and TITANIA trials showed that tozorakimab reduced the annualised rate of moderate-to-severe COPD exacerbations, debilitating attacks that signal progression of the disease, compared with placebo, when added to standard inhaled therapies.

The two studies spanned a broad range of COPD patients, including former and current smokers and people with a broad range of lung functions and levels of inflammatory eosinophil cells, and tozorakimab was "generally well tolerated," according to AZ.

The pharma groups also said that the antibody is the first in the class to show "statistically significant and highly clinically meaningful reductions in COPD exacerbations in two" phase 3 trials.

Even when on inhaled standard of care, more than 50% of patients experience exacerbations, putting them at an increased risk of serious complications that can be fatal.

The pharma industry has been looking at the potential of anti-IL-33 drugs for asthma and COPD for many years, but candidates from Sanofi/Regeneron (itepekimab) and Roche (astegolimab) have generated mixed results in clinical trials, raising questions about the role of the class in inflammatory respiratory diseases.

The landscape for COPD treatment has also started to expand beyond inhaled beta agonists, muscarinic antagonists, and corticosteroids – the mainstay of treatment for decades – after the approvals of two biologic therapies, namely Sanofi/Regeneron's IL-4 and IL-13 inhibitor Dupixent (dupilumab) and GSK's anti-IL-5 antibody Nucala (mepolizumab).

Both those drugs are approved for COPD associated so-called type 2 inflammation, generally with high eosinophil counts, so AZ's trials point potentially to a broader utility for tozorakimab if it reaches the market.

That view underpins AZ's lofty $3-$5 billion peak sales prediction for the drug, and the new data goes a long way to assuage the company's recent disappointing phase 3 results with IL-5 inhibitor Fasenra (benralizumab).

Nearly 400 million people are diagnosed with COPD worldwide, and it is the fourth-leading cause of death. By 2050, the prevalence is expected to increase to about 600 million people and become the number one cause of hospital admissions, costing global healthcare systems approximately $4 trillion.

AZ is also running two other phase 3 trials of tozorakimab in COPD, PROSPERO and MIRANDA, with readouts from both due in the first half of the year, which could set up regulatory filings in a matter of months.

Meanwhile, the drugmaker is also being tested in phase 3 for severe viral lower respiratory tract disease and in a phase 2 asthma study.