Tozorakimab may benefit adults with COPD plus bronchitis

Key takeaways:

• FEV₁, COPDCompEx event risk and mucus plugging possibly improve with receipt of anti-IL-33 monoclonal antibody tozorakimab.
• Some patient subgroups achieved more benefits in lung function with tozorakimab.

Among adults with COPD and bronchitis, receiving 600 mg of tozorakimab every 4 weeks may lead to FEV₁ improvement, according to a poster presented at the European Respiratory Society International Congress.

Tozorakimab (MEDI3506, AstraZeneca) is an anti-IL-33 monoclonal antibody, according to the poster.

“The FRONTIER-4 study results show encouraging clinical efficacy signals for tozorakimab as a potential new biologic treatment for COPD,” Dave Singh, MD, professor of respiratory pharmacology at the University of Manchester and lead investigator, told Healio. “Findings suggest that tozorakimab may improve lung function and reduces COPD worsening events, particularly in the population at high risk of future exacerbations being studied in the ongoing phase 3 LUNA program.”

In the randomized, double-blind, placebo-controlled phase 2a FRONTIER-4 study, Singh and colleagues assessed 135 current/former smokers aged at least 40 years with COPD and chronic bronchitis being treated with dual or triple inhaled maintenance therapy to see how 600 mg of tozorakimab every 4 weeks impacts pre-bronchodilator FEV₁ after 12 weeks of treatment vs. placebo.

Patients also experienced at least one exacerbation in the past 24 months, according to the poster.

Within the total cohort, 67 patients (35.8% current smokers; mean 44% predicted pre-bronchodilator FEV₁) received tozorakimab, and the remaining 68 patients (47.1% current smokers; mean 45.2% predicted pre-bronchodilator FEV₁) received placebo for 28 weeks.

Researchers reported a “numerical benefit” in pre-bronchodilator FEV₁ from baseline to week 12 among those in the tozorakimab group compared with the placebo group (least squares mean difference, 24 mL).

When divided into subgroups, tozorakimab was also more favorable than placebo for the above outcome in:

• patients who experienced at least two exacerbations in the past year (least squares mean difference, 69 mL);
• patients who experienced at least two moderate exacerbations and/or at least one severe exacerbation in the past year (least squares mean difference, 59 mL);
• patients with a blood eosinophil count (BEC) of 150 cells/μL or more (least squares mean difference, 82 mL);
• current smokers (least squares mean difference, 25 mL); and
• former smokers (least squares mean difference, 32 mL).

Evaluating time to first COPDCompEx event, which researchers explained as “a composite endpoint predictive of efficacy in reducing moderate and severe exacerbations,” revealed another positive result. At week 28, the risk for COPDCompEx events was lower in the tozorakimab group vs. the placebo group (HR = 0.79).

Subgroup analysis showed that tozorakimab was favored over placebo in most groups. Similar to above, those who had at least two exacerbations vs. at least one exacerbation in the past year from the tozorakimab group had a larger decreased risk for COPDCompEx events (HR = 0.61 vs. HR = 1), according to the poster. This outcome was also found when comparing patients who experienced at least two moderate exacerbations and/or at least one severe exacerbation vs. patients who experienced at least one exacerbation in the past year (HR = 0.64 vs. HR = 0.96).

The risk for COPDCompEx events at week 28 with tozorakimab vs. placebo was decreased to a comparable degree between those with a BEC less than 150 cells/μL (HR = 0.75) and those with a BEC of 150 cells/μL or higher (HR = 0.76). According to the poster, this was also the case between current smokers (HR = 0.86) and former smokers (HR = 0.72).

Additionally, researchers looked at changes in the baseline number of lung segments with mucus plugging in both groups at the 28-week mark and found a lower number among those receiving tozorakimab vs. placebo (least squares mean difference, –1.5).

In terms of safety, slightly more patients treated with tozorakimab reported a treatment-emergent adverse event than patients treated with placebo (79.1% vs. 73.5%). The poster also showed that a greater proportion of patients in the tozorakimab vs. placebo group reported a serious adverse event (20.9% vs. 13.2%) and adverse event of special interest (49.3% vs. 35.3%).