Evaluation of Immunogenicity in Patients with Multiple Sclerosis Treated with Daclizumab HYP (P1.147)

OBJECTIVE: Evaluate the incidence and clinical impact of immunogenicity in multiple sclerosis (MS) patients treated with daclizumab high-yield process (DAC HYP). BACKGROUND: DAC HYP is a humanized, monoclonal anti-CD25 antibody aimed at treatment of relapsing-remitting MS as a subcutaneous 150mg administration every 4 weeks. DESIGN/METHODS: DAC HYP-treated patients were evaluated for serum anti-drug antibodies (ADAs) for 2-3 years starting at baseline, Week 4, Week 12, and every 12 weeks thereafter in the DECIDE trial. ADAs were measured using a validated bridging ECL immunoassay. Assay sensitivity was 63 ng/mL with a drug:antibody tolerance of 525:1. Neutralizing antibodies (NAbs) were measured using a cell-based electrochemiluminescent assay (sensitivity <400 ng/mL) by evaluating the ability of ADAs to block binding of ruthenium-labeled DAC HYP to CD25 protein on Kit225 cells. The relationship between clinical outcomes and ADA/NAb was evaluated using descriptive statistics. RESULTS: Samples from 913 patients were evaluated. Pre-existing ADA reactivity at baseline was observed in 6[percnt] (59/913) of patients. Post-baseline ADA and NAb reactivity at any timepoint was observed in 22[percnt] (202/913) and 8[percnt] (71/913) of patients, respectively, and 19[percnt] (175/913) of ADA and all NAb responses were treatment-emergent. Most ADA-positive patients were observed during the first 24 weeks. The majority of ADA and NAb responses were transient (isolated events of <74 days in duration) and majority of these resolved after the first year. No detectable impact of ADAs/NAbs on PD responses, clinical or MRI disease activity, or adverse events was observed. CONCLUSIONS: Immunogenicity responses to DAC HYP during 3-year treatment occurred predominantly during the first 24 weeks of treatment, and were mostly transient and resolved after the first year. There was no detectable impact of immunogenicity on the safety or efficacy of DAC HYP. Study Supported by: Biogen Idec and AbbVie Biotherapeutics. Disclosure: Dr. Amaravadi has received personal compensation for activities with Biogen Idec. as an employee. Dr. Mikulskis has received personal compensation for activities with Biogen Idec as an employee. Dr. Lucas has received personal compensation for activities with Biogen Idec as an employee. Dr. Riester has received personal compensation for activities with Biogen Idec as an employee. Dr. Sweetser holds stock and/or stock options in Biogen Idec. Dr. Elkins holds stock and/or stock options in Biogen Idec.