Mirikizumab pharmacokinetics and exposure-response in pediatric patients with moderate-to-severe ulcerative colitis.

Mirikizumab is a p19-directed anti-interleukin-23 antibody approved for the treatment of adults with moderate-to-severe ulcerative colitis (UC). Here, we report the first data of mirikizumab pharmacokinetics (PK) and exposure-response (E/R) relationships in pediatric participants (aged 2 to <18 years weighing >10 kg) with moderate-to-severe UC from the phase II, open-label study SHINE-1 (NCT04004611). PK parameters were analyzed using a model developed previously in adults with fixed-exponent allometry for body weight. Serum samples collected from 26 participants during the 12-week induction and 40-week maintenance periods of SHINE-1 were analyzed. Estimated body weight-adjusted systemic clearance, volume of distribution, and subcutaneous bioavailability were 0.021 L/h, 0.069 L/kg, and 49.8%, respectively. Covariate analysis identified no clinically significant covariates other than body weight. In the exposure range studied, E/R analysis using post hoc grouping by average concentration quartile and comparison of observed change from baseline in modified Mayo Score (MMS) at Week 12 with the adult model prediction revealed no obvious E/R relationship in clinical response, clinical remission, or endoscopic response, consistent with observations in adults. The E/R relationship for observed change from baseline in MMS at Week 12 is also similar to the adult model prediction. The PK modeling and E/R analyses suggested optimal doses of intravenous mirikizumab 300 mg for weight >40 kg, 5 mg/kg for weight ≤40 kg every 4 weeks (Q4W) during induction, and subcutaneous mirikizumab 200 mg (>40 kg), 100 mg (>20 to ≤40 kg), or 50 mg (≤20 kg) Q4W during maintenance therapy for pediatric patients with moderate-to-severe UC.