OBJECTIVE: Ponezumab (PF-04360365) is a humanized anti-amyloid beta (Aβ) 
monoclonal antibody designed for treatment of Alzheimer disease (AD). A single 
2-hour intravenous infusion of 0.1 to 10 mg/kg was previously shown to be safe 
and well tolerated in subjects with mild to moderate AD, with measurable effects 
on plasma and cerebrospinal fluid Aβ. This phase I, dose-escalation, open-label 
study evaluated the safety, pharmacokinetics, and pharmacodynamics of a single 
10-minute intravenous infusion.
METHODS: Subjects with mild to moderate AD received ponezumab 1 mg/kg (n = 3), 3 
mg/kg (n = 3), 5 mg/kg (n = 4), or 10 mg/kg (n = 5). They were followed up as 
outpatients for 6 months.
RESULTS: All subjects completed the trial. Ponezumab was safe and well tolerated 
with no deaths, withdrawals, or drug-related moderate, severe, or serious 
adverse events. Mild drug-related adverse events included headache (3 patients) 
and lethargy and hypoesthesia (both in 1 patient). No infusion reactions, 
clinically meaningful laboratory abnormalities, vital sign changes, 
electrocardiographic changes, or antidrug antibodies were detected. There was no 
evidence of brain microhemorrhage, vasogenic edema, encephalitis, or other 
imaging abnormality. Cognitive function showed no treatment-related trends. 
Ponezumab displayed approximately dose-proportional increases in plasma 
exposure. Steady-state volume of distribution was 113 to 172 mL/kg, clearance 
was 2.7 to 3.0 mL/d/kg, and terminal half-life was 35 to 52 days. Plasma maximum 
observed concentration and the area under the plasma concentration-time profile 
from time 0 extrapolated to infinite time of Aβ(1-x) and Aβ(1-40) increased 
dose-dependently.
CONCLUSIONS: Administration of ponezumab as a 10-minute infusion was safe and 
well tolerated and produced effects on plasma Aβ species comparable with a 
2-hour infusion. Shorter infusions may provide more flexibility, comfort, and 
convenience for patients and caregivers.