The monoclonal antibody Tozorakimab showed significant clinical benefit in reducing COPD flare-ups for a broad range of patients, including former and current smokers.
RT’s Three Key Takeaways:
- Reduction in Exacerbations: Tozorakimab significantly reduced the annualized rate of moderate-to-severe chronic obstructive pulmonary disease exacerbations in both former and current smokers across all stages of lung function severity.
- Targeting IL-33 Pathway: As a potential first-in-class monoclonal antibody, the treatment inhibits interleukin-33 signaling to reduce inflammation and disrupt mucus dysfunction.
- Broad Patient Benefit: The Phase III trial results demonstrated clinical efficacy regardless of a patient’s blood eosinophil count, addressing a major unmet need for the nearly 400 million people living with the disease.
Positive high-level results from the Phase III OBERON and TITANIA clinical trials show that tozorakimab significantly reduced the annualized rate of moderate-to-severe COPD exacerbations compared to placebo, according to AstraZeneca.
The trial results demonstrated clinical benefit in the primary population of former smokers, as well as the overall population that included current smokers and patients across all stages of lung function severity. The drug was generally well tolerated with a favorable safety profile, according to the news release.
Tozorakimab is a potential first-in-class monoclonal antibody that targets interleukin-33 (IL-33). It uniquely inhibits the signaling of both the reduced and oxidized forms of IL-33, which allows the treatment to both decrease inflammation and disrupt the cycle of mucus dysfunction, according to the news release.
COPD is a progressive disease and the third leading cause of death globally. Even when using inhaled standard of care treatments, more than 50% of patients still experience exacerbations that increase the risk of mortality and cardiopulmonary events. In the OBERON and TITANIA trials, patients received 300mg of tozorakimab or a placebo once every four weeks in addition to their standard inhaled healthcare.
“These trial results suggest that targeting the IL-33 pathway with tozorakimab delivers meaningful clinical benefit in a trial representing a broad COPD population, independent of smoking status and eosinophilic levels,” said Frank Sciurba, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the LUNA programme, in a news release.
Sciurba added that COPD has long been a difficult-to-treat disease with significant unmet need, noting that up to half of patients worldwide are at risk of hospitalizations and death.
“Tozorakimab works in a fundamentally different way from other biologics, inhibiting the signalling of the reduced and oxidised forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction that are key disease drivers in COPD,” said Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, in a news release.
AstraZeneca plans to share the full results from the OBERON and TITANIA trials at an upcoming medical meeting. The company is also conducting additional Phase III trials for the drug in COPD, known as PROSPERO and MIRANDA, and is studying the therapy for use in asthma and severe viral lower respiratory tract disease.
