D1.456 - Integrated Analysis of Nemolizumab Immunogenicity Indicates No Effect on the Overall Benefit-Risk Profile of Nemolizumab in Patients with Atopic Dermatitis or with Prurigo Nodularis

Therapeutic proteins, including biologics, can trigger unwanted immune responses, producing anti-drug antibodies (ADA) that may affect the pharmacokinetics (PK), pharmacodynamics, safety, or efficacy of the drug. Nemolizumab is a humanized IgG2 monoclonal antibody that blocks interleukin-31 by binding to its receptor (IL-31RA). Nemolizumab  is approved for the treatment of atopic dermatitis (AD) and prurigo nodularis (PN) in several countries including North American and European countries. Nemolizumab is intended for long-term use. Its immunogenicity potential was assessed using an integrated multidisciplinary approach, including risk assessment, bioanalytical methods suitability and clinical immunogenicity-related findings.

ADA were assessed using a validated electro chemiluminescence immunoassay. Confirmed ADA samples underwent titration dilution assay to assess the circulating ADA abundance and were further tested using a validated cell-based assay to assess their neutralizing capacity.

Immunogenicity clinical data: ADA and neutralizing antibodies (Nab) were assessed in 1100 patients with AD and in 358 patients with PN enrolled in phase 3 studies. The median treatment duration ranged from 14 to 17 months in PN and AD indications, respectively.

In the phase 3 AD pivotal (ARCADIA 1, ARCADIA 2) and long-term extension (LTE) studies  with up to 2.5 years of follow-up, treatment-emergent ADA occurred in 11.2% of patients, while Nab were detected  in 0.5% of patients.

In the phase 3 PN pivotal (OLYMPIA 1, OLYMPIA 2) and LTE studies with up to 2.2 years of follow-up, treatment-emergent ADA occurred in 12.8% of patients, while Nab were detected  in 3.5% of patients.

Impact of immunogenicity on PK, efficacy and safety: Mean nemolizumab serum levels remained consistent over time, regardless of ADA status in both indications. Efficacy and the incidence of adverse events (AEs) were similar between ADA-positive and ADA-negative patients, with no clinically meaningful differences observed in different AE categories. No significant differences were found between ADA-positive and ADA-negative patients, likely due to the low incidence of treatment-emergent ADA.

There was no discernable impact of immunogenicity on the overall clinical benefit and risk of nemolizumab according to the integrated immunogenicity analysis performed on a robust dataset of 1458 patients with either AD or PN followed for more than 2 years.