Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer’s Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study

Article type: Research Article

Authors: Salloway, Stephen P.^{a; #} | Sperling, Reisa^{b; #} | Fox, Nick C.^c | Sabbagh, Marwan N.^{d; 1} | Honig, Lawrence S.^e | Porsteinsson, Anton P.^f | Rofael, Hany^g | Ketter, Nzeera^{g; 2} | Wang, Daniel^g | Liu, Enchi^{g; 3} | Carr, Stephen^g | Black, Ronald S.^{h; 4} | Brashear, H. Robert^{i; *}

Affiliations: [a] Brown Medical School, Butler Hospital, Providence, RI, USA | [b] Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, MA, USA | [c] Dementia Research Centre, University College London, Institute of Neurology, London, UK | [d] Barrow Neurological Institute, Phoenix, AZ, USA | [e] Columbia University, New York, NY, USA | [f] University of Rochester School of Medicine and Dentistry, Rochester, NY, USA | [g] Janssen Alzheimer Immunotherapy Research & Development, LLC, South San Francisco, CA, USA | [h] Pfizer Inc, Collegeville, PA, USA | [i] Janssen Research & Development LLC, Pennington, NJ, USA

Correspondence: [*] Correspondence to: H. Robert Brashear, Janssen Research & Development, 1800 American Boulevard, Pennington, NJ 08534, USA. Tel.: +1 609 730 2501; Fax: +1 609 730 2069; E-mail: [email protected].

Note: [1] Present address: Cleveland Clinic Lou Ruvo Center for Brain Health888 W Bonneville Ave., Las Vegas, NV, USA.

Note: [2] Present address: 141 Leland Avenue, Menlo Park, CA, USA.

Note: [3] Present address: Prothena Biosciences Inc., South San Francisco, CA, USA.

Note: [4] Present address: 1625 Paper Mill Rd., Meadowbrook PA, USA.

Note: [#] These authors contributed equally to this work.

Abstract: Background:A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer’s disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. Objectives:The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of efficacy of bapineuzumab. Methods:A multicenter study in patients who had participated in double-blind placebo-controlled parent studies. Patients enrolled in the extension study were assigned to receive IV infusions of bapineuzumab (0.5 or 1.0 mg/kg) every 13 weeks until termination but were blinded to whether they had received bapineuzumab or placebo in the parent studies. Results:A total of 1,462 (688 were APOE ɛ4 carriers and 774 were noncarriers) patients were enrolled. Extension-onset adverse events occurred in >81% of the patients in each dose group. Fall, urinary tract infection, agitation, and ARIA-E occurred in ≥10% of participants. The incidence proportion of ARIA-E was higher among carriers and noncarriers who received bapineuzumab for the first time in the extension study (11.8% and 5.4%, respectively) versus those who were previously exposed in the parent studies (5.1% and 1.3%, respectively). After 6 to 12 months exposure to bapineuzumab IV in the extension study, similar deterioration of cognition and function occurred with no significant differences between the dose groups. Conclusions:Infusion of bapineuzumab 0.5 or 1.0 mg/kg every 13 weeks for up to 3 years was generally well tolerated, with a safety and tolerability profile similar to that in previous studies.

Keywords: Alzheimer’s disease, amyloid-related imaging abnormality with edema/effusions, bapineuzumab, long-term safety

DOI: 10.3233/JAD-171157

Journal: Journal of Alzheimer's Disease, vol. 64, no. 3, pp. 689-707, 2018