Open AccessPhase II Dose Selection for Alpha Synuclein–Targeting Antibody Cinpanemab (BIIB054) Based on Target Protein Binding Levels in the Brain
Author(s) -
Kuchimanchi Mita,
Monine Michael,
Kandadi Muralidharan Kumar,
Woodward Caroline,
Penner Natalia
Publication year - 2020
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12538
Subject(s) - pharmacokinetics , tolerability , monoclonal antibody , pharmacology , in vivo , medicine , antibody , population , alpha synuclein , parkinson's disease , disease , immunology , adverse effect , biology , microbiology and biotechnology , environmental health
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.