title: Ethnic sensitivity assessment of pharmacokinetics and pharmacodynamics of omalizumab with dosing table expansion.
abstract: A three-part license expansion for omalizumab (Xolair(®)), humanized anti-IgE antibody, was recently made in Japan for paediatric use, additional higher doses and revised dosing frequency in allergic asthma. The dosing level and frequency of omalizumab are guided by a dosing table based on the total serum IgE and bodyweight. Nonlinear mixed-effect pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation techniques described the binding between omalizumab and its target IgE. The population PKPD analysis was conducted using data from the nine studies included originally in the European application of dosing table expansion together with three Japanese clinical studies to assess the influence of the ethnicity. Statistically significant differences between the ethnic groups were detected. These were small, within or close to bioequivalence criteria. The model described the primary pharmacology in Caucasian and Japanese patients, both adult and paediatric, with simulations showing that the interplay between the clearance, volume and binding affinity parameters was such that there was no clinical impact of the Japanese ethnic differences on either drug PK or free IgE suppression and hence the required posology.
authors.affiliation: Novartis Pharma K.K., 1-23-1 Toranomon, Minato-ku, Tokyo 105-6333, Japan. Electronic address: wataru.honma@novartis.com.
authors.forename: Wataru
authors.initials: W
authors.lastname: Honma
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland. Electronic address: aurelie.gautier@novartis.com.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gautier
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland. Electronic address: ines.paule@novartis.com.
authors.forename: Ines
authors.initials: I
authors.lastname: Paule
authors.affiliation: Novartis Pharma K.K., 1-23-1 Toranomon, Minato-ku, Tokyo 105-6333, Japan. Electronic address: masayuki.yamaguchi@novartis.com.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland. Electronic address: phil.lowe@novartis.com.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lowe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D044466:Asian People; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007564:Japan; D008875:Middle Aged; D008954:Models, Biological; D000069444:Omalizumab / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D044465:White People; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D000069444:Omalizumab; D007073:Immunoglobulin E
keywords: Allergic asthma; Anti-immunoglobulin E; Dosing table; Modeling and simulation; Omalizumab