Anti-drug antibody titer may guide neutralizing antibody testing

AIMS: To evaluate neutralizing antibodies (NAb) against insulin icodec and explore whether an anti-drug antibody (ADA) titer threshold can guide clinically meaningful NAb testing. PATIENTS AND METHODS: A cell-based insulin icodec NAb assay was developed and applied to follow-up samples collected after 6 weeks of drug wash-out from two treat-to-target trials in insulin-naïve patients with type 2 diabetes. ADA status and titers, NAb status, efficacy, and safety outcomes were evaluated. RESULTS: Of 355 follow-up samples, 270 (76%) were ADA positive and 35 (9.9%) were NAb positive. Neither ADA nor NAb status was associated with safety or efficacy concerns. The rate of NAb positivity increased with ADA titer. A titer threshold of 200 improved reliability and interpretability and reduced the number of samples requiring NAb testing by 68%. A higher threshold would be required during active treatment because of residual drug interference. CONCLUSIONS: NAb testing. When NAb testing is required, an appropriate ADA titer threshold should guide sample selection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov IDs NCT03751657 and NCT04795531.