Assessment of Minipigs as a Non-clinical Model for Screening and Derisking Injection Site Reactions in Clinical Trials.

purposeInjection site reactions (ISRs), including edema, erythema, pruritus, and pain, impact patient experience and drug tolerability. ISRs are commonly observed and pose challenges in therapeutic development, yet no non-clinical model exists for screening and derisking them before human trials. To fill in this gap, we sought to evaluate the minipig as a non-clinical model for ISRs.

methodsThe minipig model was assessed using six ISR-inducing molecules (positive controls) and two placebos with matching formulations (negative controls). Additionally, to evaluate the physiological similarity between minipigs and humans, we tested whether antihistamine pre-treatment, which is known to reduce ISRs in humans, had a similar effect in minipigs.

resultsThe minipig model consistently responded to all six positive control molecules, though at higher doses than in humans. Minor ISRs occurred in a quarter of the negative controls but their frequency and/or severity was easily distinguishable from positive controls. Antihistamine pre-treatment effectively reduced ISR severity.

conclusionOur results suggest that the minipig model shows promise for non-clinical screening of high-risk molecules. If a molecule consistently triggers ISRs in the minipig model, phase-appropriate derisking and/or mitigation strategies are warranted. We note that the minipig model is often used for other purposes during pre-clinical subcutaneous drug development; therefore, adding ISR readouts to existing studies would incur minimal operational burden and cost. In summary, our results indicate the potential value of the minipig model in pre-clinical ISR risk assessment.