Safety and Pharmacology of a Single Intravenous Dose of Ponezumab in Subjects With Mild-to-Moderate Alzheimer Disease

Abstract

A 2-hour infusion of 0.1 to 10 mg/kg ponezumab was well tolerated in subjects with mild-to-moderate AD. Plasma pharmacokinetic profile was approximately linear. Plasma Aβ increased with dose, and CSF Aβ increased at the highest dose, suggesting that intravenous ponezumab alters central Aβ levels.

Tau immunotherapy for Alzheimer's disease

“…In related studies, it is surprising how limited PK/PD data have been presented for the Ab immunotherapy trials. The most detailed PK/PD study for a CNS therapeutic antibody to date was for Ponezumab, and indicated that its CNS concentration was approximately 0.1% of peripheral exposure [4,90]. Data from microdialysis studies in P301S mice…”

Antibody Therapeutics Targeting Aβ and Tau

“…Following these encouraging studies in mice, a phase I clinical trials was initiated. Reportedly, Ponezumab increased plasma and CSF Aβ 40 levels in a dose dependent fashion with minimal adverse effects (Burstein et al 2013; Landen et al 2013). Similarly, a phase II trial demonstrated increased plasma Aβ 40 levels with good tolerance.…”

Alzheimer’s Disease: Dawn of a New Era?

“…Ponezumab (PF-04360365) is a humanized IgG2δA monoclonal antibody that unlike the other monoclonal antibodies binds the free carboxyl terminal of amino acids 33-40 of the Aβ 1-40 peptide (72). Five phase I trials showed acceptable safety but two phase II trials concluded in 2011 showed no treatment effect and development of ponezumab for AD is no longer being pursued although its use is being explored in patients with cerebral amyloid angiopathy.…”