FRONTIER3: Tozorakimab Shows Signal in Early-Onset Asthma

Key Takeaways

• In the intent-to-treat population, the week 16 primary endpoint was not statistically significant versus placebo.
• Patients with at least 2 prior exacerbations showed greater improvement in clinic pre-BD FEV1, especially with 600 mg.
• A total of 235 adults were randomized 1:1:1 to tozorakimab 600 mg, tozorakimab 300 mg, or placebo every 4 weeks, and tozorakimab was well tolerated.

Among adults with moderate-to-severe early-onset asthma receiving standard care, anti-IL-33 monoclonal antibody tozorakimab missed the primary endpoint overall, but the 600 mg dose showed a 212 mL least-squares mean advantage over placebo in clinic pre-bronchodilator FEV1 at week 16 among patients with at least 2 prior exacerbations.

In FRONTIER-3, investigators conducted a randomized phase 2a study in adults with moderate-to-severe early-onset asthma receiving standard care. The intent-to-treat population included 235 patients randomized 1:1:1 to tozorakimab 600 mg, tozorakimab 300 mg, or placebo given subcutaneously every 4 weeks subcutaneously. Both active doses were compared with placebo while patients remained on background therapy. Median disease duration exceeded 30 years, and most participants had baseline blood eosinophil counts below 300 cells/µL. The primary endpoint was change from baseline to week 16 in clinic pre-bronchodilator FEV1.

At week 16, neither tozorakimab dose produced a statistically significant improvement in clinic pre-BD FEV1 versus placebo in the overall population. For 600 mg, the least-squares mean difference was 4 mL, with an 80% confidence interval from -71 to 79. That estimate remained close to placebo, and the corresponding p value was 0.473. For 300 mg, the least-squares mean difference was 36 mL, with an 80% confidence interval from -38 to 111 and p=0.267. Across both dose groups, these effects did not produce a statistically significant result for the primary analysis.

Among patients with at least 2 prior exacerbations, clinic pre-BD FEV1 improved more versus placebo, with the stronger 600 mg signal already noted. In this subgroup, 300 mg was associated with a 77 mL least-squares mean difference, with an 80% confidence interval from -34 to 187 and p=0.186. Improvements in home FEV1 and home peak expiratory flow were also greater than in the overall intent-to-treat population.