The Göttingen minipig® as an alternative non-rodent species for immunogenicity testing: a demonstrator study using the IL-1 receptor antagonist anakinra.

The use of recombinant human proteins for the treatment of several diseases has increased considerably during the last decades. A major safety and efficacy issue of biopharmaceuticals is their potential immunogenicity. To prevent immunogenicity, biotechnology-derived proteins are engineered to be as human-like as possible. Immunogenicity is mainly determined in non-human primates (NHP), as they are considered to be the best predictive animal species for human safety, based on their close relatedness to man. As minipigs are increasingly used in the safety evaluation of (bio)pharmaceuticals, the predictive value of the minipig in immunogenicity testing was evaluated in this study, using anakinra as a model compound. Animals were treated subcutaneously with either placebo, low- (0.5 mg/kg), or high-dose (5 mg/kg) anakinra daily on 29 consecutive days. After the first and last dose, the pharmacokinetic (PK) profile of anakinra was evaluated. Antibodies directed to anakinra were measured on several time points during the treatment period. Furthermore, hematology, clinical chemistry, body weight, clinical signs, and histopathology of several organs were evaluated. No signs of toxicity were observed upon treatment with anakinra. PK parameters were comparable with those found in human and NHP studies performed with anakinra. All animals developed anti-anakinra antibodies. The results obtained in minipigs were comparable to those observed in monkeys. For anakinra, the predictive value of the minipig for immunogenicity testing was found to be comparable to that seen in NHP. However, more studies evaluating additional biopharmaceutical products are needed to support the use of the minipig as an alternative model for (immuno)toxicity testing, including immunogenicity.