1741-P: Efficacy and Safety of Inhaled Technosphere Insulin (TI) vs. Rapid-Acting Analog in Youth with HbA1c ≤9.5%: Subgroup Analysis from INHALE-1

Introduction and Objective: Technosphere Insulin (TI) is an inhaled, ultra-rapid, prandial insulin. The INHALE-1 study enrolled youth with type 1 or type 2 diabetes with baseline HbA1c 7.0 to 11.0%. This analysis focuses on participants with baseline HbA1c ≤9.5%, a threshold commonly used in pediatric prandial insulin trials, which may reduce confounding from severe dysglycemia, barriers to medication taking, and insulin resistance, and to better isolate prandial insulin effects on glycemic endpoints. Methods: Participants aged 4-17 were randomized to TI plus basal insulin or rapid-acting insulin analog (RAA) plus basal insulin for 26 weeks. Change in baseline HbA1c to Week 26 was assessed using ANCOVA, with a non-inferiority margin of 0.4% for the upper limit of the 95% confidence interval (CI). Safety and continuous glucose monitoring (CGM) metrics were also compared. Results: Participants with baseline HbA1c ≤9.5% (N=209; TI: 106, RAA: 103) were included. At Week 26, least squares (LS) mean change in HbA1c was 0.19% (95% CI: 0.007, 0.365) for TI and 0.08% (95% CI: -0.103, 0.256) for RAA. The LS mean difference (TI-RAA) was 0.11% (95% CI: -0.145, 0.364), meeting non-inferiority (CI upper limit <0.4%). In the overall intent-to-treat INHALE-1 population (N=230; TI: 117, RAA: 113), non-inferiority was not met. The sensitivity analysis showed that, after excluding one participant who did not follow the study protocol, the results met the non-inferiority criteria. Pulmonary function remained stable and CGM (including hypoglycemia) metrics were similar between groups. Conclusion: Among youth with baseline HbA1c ≤9.5%, inhaled TI demonstrated comparable efficacy and safety to RAA, supporting TI as an alternative prandial insulin option for youth with diabetes. When considering therapy options, it’s essential to align treatment with the patient’s preferences, readiness, and goals. Their engagement and comfort with the chosen therapy may contribute to achieving successful outcomes. Disclosure K. Kaiserman: Employee; Current; MannKind Corporation. Stock/Shareholder; Current; MannKind Corporation. J. Sylvan: Employee; Current; MannKind Corporation. L.E. Mycue: Employee; Current; MannKind Corporation. J.K. Rinker: Employee; Current; MannKind Corporation. J. Nguyen: Other - Post-Doctoral Fellow (Contractor); Current; MannKind Corporation. J.T. Rittenberry: Employee; Current; MannKind Corporation.