Name:	Bapineuzumab
Other Names:	AAB-001
Therapeutic Applications:	Mild to moderate Alzheimer disease.
Therapy Types:	Protein: humanized monoclonal antibody against Aβ.
Mechanisms:	Designed to bind and remove the Aβ peptide that accumulates in the brain.
Development Status:	investigational in U.S.
FDA Phase:	Phase III
Primary Medical Role:	Immunotherapy approaches to the treatment of Alzheimer disease is based on the ability of antibodies raised against Aβ peptides to bind to and clear Aβ from the brain, thus removing the peptide and inhibiting the damage to neurons that Aβ inflicts. Bapineuzumab is a passive immunotherapy approach, in which patients are treated with humanized monoclonal antibodies with specificity to Aβ peptides. The treatment with antibodies should bind and clear Aβ, with the potential added benefit of a better safety and tolerability profile.
Role in Alzheimer's Disease:	Results from Phase II were reported at ICAD 2008. (See ARF related news story.) This 18 month study was a double-blind, placebo-controlled multiple ascending dose trial intended to primarily assess the safety, tolerability and secondarily, efficacy of bapineuzumab in mild-to-moderate Alzheimer Disease and had 234 patients randomized to receive one of four doses of bapineuzumab (0.15 mg/kg [n=31], 0.5 mg/kg [n=33], 1.0 mg/kg [n=30] or 2.0 mg/kg [n=30]) or placebo [n=110] by intravenous infusion every 13 weeks. Efficacy endpoints were change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Disability Assessment Scale for Dementia (DAD) the Neuropsychological Test Battery (NTB), the Clinical Dementia Rating Sum of Boxes (CDR-SB) and brain volume as measured by MRI. Efficacy was assessed from baseline for 78 weeks. In ApoE4 non-carriers, statistically significant differences were observed in favor of bapineuzumab treated patients on both cognitive and functional efficacy endpoints ADAS-Cog, NTB and CDR-SB. In the ApoE4 carrier patients, no statistically significant changes were observed in any of the cognitive or functional efficacy endpoints.
Pharmacological Role:	Anti-Aβ antibodies have been shown to prevent the accumulation of Aβ peptides in the brains of transgenic mouse models of AD (Shenk et al., 1999; Bard et al., 2000; DeMattos et al., 2001). Anti-Aβ immunotherapy has been further shown to reverse cognitive decline in transgenic mice (Morgan et al., 2000). In one clinical trial, patients immunized with Aβ peptide who actively generated anti-Aβ antibodies showed a significantly slower rate of decline in cognitive functions (Hock et al., 2003).
Side Effects:	Adverse effects of Bapineuzumab were generally mild and transient. The most severe and the only dose-related side effect observed in the Phase II study was vascular edema. Twelve (12) cases of vasogenic edema were reported, all in treated patients, and all resolved over time. Ten (10) of these cases were reported in ApoE4 carriers with 2 cases in ApoE4 non-carriers. Eight (8) of the 12 cases were reported in the highest dose group, including both cases seen in ApoE4 non-carriers. As a consequence of this dose-related AE, the highest dose (2.0 mg/kg) will not be tested in Phase III studies. See ARF related news story for further details.
Companies:	Elan Pharmaceuticals, Inc., Wyeth
Notes:	Wyeth and Elan are currently are listing eight open Phase III and one open Phase II clinical trials to test Bapineuzumab in patients with mild to moderate AD. For further details, see Bapineuzumab Open Trials. This entry was updated October 22, 2009.

References

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