title: Population-based efficacy modeling of omalizumab in patients with severe allergic asthma inadequately controlled with standard therapy.
abstract: Omalizumab, a recombinant humanized monoclonal antibody, is the first approved anti-immunoglobulin E (IgE) agent for the treatment of subjects with moderate to severe persistent allergic asthma that are inadequately controlled by the standard of care. The objective of this study was to quantitatively characterize relationships between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) as well as serum free IgE and airway inflammation (as measured by fractional exhaled nitric oxide [FeNO]) using population-based efficacy models. Data were collected from patients in the EXTRA trial who received omalizumab or placebo 150 to 375 mg subcutaneously every 2 or 4 weeks from week 0 to 48 with constant standard of care as background therapy. None of the covariates evaluated, including demographics, disease status, and baseline pharmacodynamic biomarkers, were significant in explaining the variability in the FEV1 or FeNO response to omalizumab. Results from the efficacy models further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml and quantified the variability for the target. In addition, the resulting population models could be used to predict population FEV1 or FeNO response for omalizumab and/or other anti-IgE therapeutics for which PK-IgE models are constructed.
authors: Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
authors: Rui
authors: R
authors: Zhu
authors: Yanan
authors: Y
authors: Zheng
authors: Wendy S
authors: WS
authors: Putnam
authors: Jennifer
authors: J
authors: Visich
authors: Mark D
authors: MD
authors: Eisner
authors: John G
authors: JG
authors: Matthews
authors: Karin E
authors: KE
authors: Rosen
authors: David Z
authors: DZ
authors: D'Argenio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D002648:Child; D003198:Computer Simulation; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D009569:Nitric Oxide / Q000378:metabolism; D000069444:Omalizumab; D011446:Prospective Studies; D013147:Spirometry; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069444:Omalizumab; D009569:Nitric Oxide; D007073:Immunoglobulin E