Background Canakinumab (CAN) has demonstrated efficacy in patients with Cryopyrin-Associated Periodic Syndromes (CAPS) ≥2 yrs of age1. However, no information on the pharmacokinetics (PK) of CAN in patients 2 yrs of age is available. We present preliminary PK data from a phase III study in this patient population.
Objectives Primary objective was to assess the efficacy of CAN with respect to the treatment response in CAPS patients ≤4 yrs of age. A secondary endpoint was to evaluate PK and pharmacodynamics (PD) profiling of CAN.
Methods CAN-naïve patients with confirmed CAPS aged 44 days to 4 yrs received open-label CAN dosed 2-12 mg/kg every 4 or 8 weeks for 56 weeks. For NOMID patients, an initial dose of 4 mg/kg was administered. Patients who did not achieve complete response following CAN injection, or experienced a flare before the next planned administration, were eligible for dose up-titration with possible maintenance and step-wise up-titration regimens of 4, 6, 8, 10, or 12 mg/kg s.c.
Results Seventeen patients, 6 patients <24 months old (44 days to 14 months; mean age =7 month), were enrolled and administered body weight-based (2 mg/kg to 10 mg/kg) doses of CAN s.c. every 8 weeks, with the exception of one patient who received doses of 4-6 mg/kg once weekly. Patients received more than one dose during the study. Of the 6 patients <24 months old, 5 were dosed with 2 mg/kg at each dose, 1 NOMID patient started with 4 mg/kg and up-titrated to 8 mg/kg at last dose. The efficacy observed in this trial was consistent with efficacy reported in studies of older patients. Sixteen patients achieved a complete response, with 7 patients requiring dose escalation to achieve and/or maintain their responses. Dose-normalized mean CAN trough concentrations at steady-state (Css, trough) in the patients <24 months old were similar across the 6 patients from 44 days to 15 months, while the range of exposures as represented by the dose-normalized trough levels (Css,trough) overlapped with the remaining 11 study patients >2 yrs old who received CAN doses ranging from 2–10 mg/kg. The safety profile for patients <24 months was similar to that observed for older patients and the overall study safety profile was similar to that observed in the pivotal program.
Conclusions Canakinumab is a highly effective treatment for patients with CAPS aged as young as 44 days old. The preliminary PK results demonstrated that dose-normalized canakinumab exposure in patients <2 yrs old was similar to patients >2 yrs supporting the utilization of weight-based dosing in the CAPS infantile population.
Lachmann H, et al. N Engl J Med. 2009;60:2416-25.
Disclosure of Interest J. Kalabus Employee of: Novartis, Y. Uziel Consultant for: Novartis, Speakers bureau: Novartis, P. Brogan Grant/research support from: Institutional grant support to undertake the study described in this abstract, Consultant for: SOBI and Roche, M. Hofer Consultant for: Novartis, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, B. Lauwerys: None declared, A. Speziale Employee of: Novartis, R. Laxer Grant/research support from: Database funding from Novartis, Consultant for: Participant in Ad Board for Novartis, H. Lachmann Consultant for: Novartis, Speakers bureau: Novartis, H. Sun Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Leon Employee of: Novartis, G. Junge Employee of: Novartis