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P580. A comparison of the pharmacokinetics of IMA-638, an anti-IL-13 monoclonal antibody, among healthy volunteers, subjects with asthma and ulcerative colitis patients

W. Reinisch1, F. Hua2, J. Panes3, K. Page2, G.M. Comer2, F. Cataldi2, 1Medical University of Vienna, Internal Medicine/Gastroenterology, Vienna, Austria, 2Pfizer Inc., Gastroenterology, Cambridge, United States, 3Hospital Clinic I Provincial, Department of Inflammatory Disease, Barcelona, Spain

Background

Anrukinzumab-IMA-638 (IMA) is a humanized antibody (IgG1) that binds and inhibits human IL13. It has been evaluated for both asthma and ulcerative colitis. Since changes in drug exposure in different patient population could lead to different treatment paradigms, the objective of the current report is to compare PK properties for IMA-638 in different populations.

Methods

Clinical studies in which complete PK profiles were available were included in the comparison. A total of 4 studies were included in the analysis. They are: (1) Single ascending dose (SAD) study with both intravenous and subcutaneous administration in mild to moderate asthma patients, the dose range was 0.3–4 mg/kg for SC and 3 mg/kg for IV with 8 subjects (2 placebo + 6 active) per cohort; (2) Single ascending dose study with subcutaneous administration in healthy Japanese and non-Asian volunteers, the dose range was 0.3–4 mg/kg with 8 subjects (2 placebo + 6 active) per cohort; (3) Allergen challenge study with two 2 mg/kg doses subcutaneous administered at 1 week apart in subjects with mild atopic asthma, a total of 14 subjects with PK parameters available; (4) Proof of mechanism study with 5 dose intravenous administration at 200, 400 and 600 mg levels in ulcerative colitis patients, a total of 59 subjects with PK parameters available. Serum concentration of IMA-638 was analyzed using the same validated enzyme-linked immunosorbent (ELISA) assay for all the studies. Non-compartmental analysis was used to derive PK parameters.

Results

The exposure of IMA-638 exhibited approximately dose-proportional increase for the dose rage tested in the two SAD studies. PK parameters appeared to be similar between Japanese and non-Asian populations based on study 2. Terminal half-life was similar for sc and IV administration based on study 1 with asthma patients, which is around 25 days. Terminal half-life was also similar when compared healthy volunteer to asthma patients based on study 1, 2 and 3. However, when comparing UC patients to other population, the half-life was reduced to 15–20 days. The clearance was increased by roughly 2 fold in UC patients (0.010–0.013 L/h) compared with asthma patients (0.00551 L/h) with IV administration of IMA-638. The volume of distribution was similar in UC patients (5.3–7.0 L) and asthma patients (5.09 L).

Conclusion

IMA-638 appears to have shorter half-life in ulcerative colitis patients compared with either healthy volunteers or subjects with asthma. The shorter half-life is due to faster clearance while the volume of distribution appears to be similar among different populations.