Ponezumab in mild‐to‐moderate Alzheimer's disease: Randomized phase II PET‐PIB study

Abstract

IntroductionThe safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year.MethodsSubjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively.ResultsPonezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected.ConclusionsBoth ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.

BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

“…Ponezumab entered phase I studies and displayed evidence of safety and tolerability in mild to moderate patients with AD, without signs of ARIA . Yet, the lack of clinical efficacy was the reason to terminate the studies after phase II trial …”

“…112 Yet, the lack of clinical efficacy was the reason to terminate the studies after phase II trial. 125 Consequently, studies over second generation anti-Aβ mAbs have taken place due to the disappointing observations from the first-generation mAbs. Gantenerumab (RG1450/RO4909832, Hoffman-La Roche), is the first fully human IgG1 antibody that targets the fibrillary Aβ form and uniquely binds the epitope that involves both, the N-terminal (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and mid-region (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) residues.…”

Neuroprotective Approach of Anti-Cancer Microtubule Stabilizers Against Tauopathy Associated Dementia: Current Status of Clinical and Preclinical Findings

“…Gantenerumab, a fully human monoclonal antibody that binds aggregated A␤ and removes A␤ plaques by Fc receptor-mediated phagocytosis, is in the Phase III recruiting stage [121,122]. Some other monoclonal antibodies which are recently observed are BAN-2401 [123,124]; UB-311 [125,126]; Crenezumab [127,128]; Ponezumab [129,130]; Octagam [131,132]; SAR-228810 [133,134]; MEDI-1814 [135]; KHK-6640 [136,137]; Lu-AF-20513 [138][139][140] and TTP4000 [133,141]. Some approaches to inhibition of enzymes, i.e., ␤and ␥-secretases involved in A␤PP cleavage, resulted in A␤ peptide formation.…”

Alzheimerio ligos gydymo metodų paieška: klinikinių tyrimų kryptys

“…Ta èiau 2017 m. bir þe lio më ne sá pa skelb to klini ki nio ty ri mo re zul ta tai pa ro dë, kad, nors vais tas bu vo gerai to le ruo ja mas, per ëji mas per he ma to en ce fa li ná bar je rà bu vo ne di de lis, taip pat vais tas ne su ma þi no nei bio mar keriø kie kio sme ge nø skys ty je, nei ami loi do san kau pø smege ny se ir ne tu rë jo áta kos kli ni ki nëms cha rak te ris ti koms. Kli ni ki niai ty ri mai bu vo nu trauk ti [35].…”

“…Adu ka nu ma bo, se lek ty viai vei kian èio ag reguo tà ami loi dà, tei gia mi re zul ta tai pa re mia ami loi do kaska dos hi po te zae. Nors ir ne sëk min gi, ki tø vais tø ty ri mai sutei kë þi niø apie kiek vie no vais to vei ki mo me cha niz mà ir ga li mai at ei ty je pla nuo ja mà vais tø de ri ni mà, vei kiant ke lis pa to ge ne zi nius pro ce sus [34,35].…”