Phase II Dose Selection for Alpha Synuclein-Targeting Antibody Cinpanemab (BIIB054) Based on Target Protein Binding Levels in the Brain.

Autor: Kuchimanchi M; Clinical Pharmacology & Pharmacometrics, Biogen Inc., Cambridge, Massachusetts, USA., Monine M; Clinical Pharmacology & Pharmacometrics, Biogen Inc., Cambridge, Massachusetts, USA., Kandadi Muralidharan K; Clinical Pharmacology & Pharmacometrics, Biogen Inc., Cambridge, Massachusetts, USA., Woodward C; Clinical Pharmacology & Pharmacometrics, Biogen Inc., Cambridge, Massachusetts, USA., Penner N; Clinical Pharmacology & Pharmacometrics, Biogen Inc., Cambridge, Massachusetts, USA.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2020 Sep; Vol. 9 (9), pp. 515-522. Date of Electronic Publication: 2020 Aug 19.
DOI: 10.1002/psp4.12538
Abstrakt: This modeling and simulation analysis was aimed at selecting doses of cinpanemab (BIIB054), a monoclonal antibody targeting aggregated α-synuclein, for a phase II study in Parkinson's disease (PD). Doses and regimens were proposed based on anticipated target concentration in brain interstitial fluid (ISF); in vitro/in vivo data on the affinity of monoclonal antibodies to the target protein; and safety, tolerability, and pharmacokinetic data (1-135 mg/kg intravenous administration) from a phase I single ascending dose (SAD) study. A population pharmacokinetic modeling approach was used to select intravenous doses of 250, 1,250, and 3,500 mg every 4 weeks, to maintain 50%, 90%, and > 90% of target binding in ISF of PD participants. A favorable safety profile from the SAD study-which showed that cinpanemab was generally well-tolerated at doses up to 90 mg/kg, supported by modeling and simulations of the anticipated safety margins-allowed implementation of a fixed-dose approach.
(© 2020 Biogen. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, LLC. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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