Name:	Bapineuzumab
Other Names:	AAB-001
Therapeutic Applications:	Mild to moderate Alzheimer disease
Therapy Types:	Immunotherapy. 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.
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. In March 2010, imaging analysis of AD patients demonstrated that bapineuzumab reduces cortical PiB retention, a measurement of fibrillar plaque (Rinne et al 2010).
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:	In Phase II trials, adverse effects of Bapineuzumab were generally mild and transient. The most severe and the only dose-related side effect observed in Phase II studies was vasogenic edema, an abnormal accumulation of fluid in the brain which is also called (ARIA)-E . Twelve cases of vasogenic edema were reported, all in treated patients, and all resolved over time. Ten of these cases were reported in ApoE4 carriers with 2 cases in ApoE4 non-carriers. Eight 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 side effect, the highest dose (2 mg/kg) will not be tested in Phase III studies. See ARF related news story for further details. In April 2009, the highest bapineuzumab dose (2 mg/kg) was dropped in APOE ε4 non-carriers because of the risk of vasogenic edema; the patients were dosed instead with 1 mg/kg.
Companies:	Janssen Alzheimer Immunotherapy
Notes:	In August 2012 Phase III clinical trials of intravenous bapineuzumab were halted in patients with mild to moderate Alzheimer’s disease due to disappointing results. See ARF related news story and ARF related news story. For clinical trials of Bapineuzumab on clinicaltrials.gov see Bapineuzumab trials. This entry was updated August 13, 2012.

References

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