Elan Corporation, plc and Wyeth announced encouraging preliminary findings from a phase II study of bapineuzumab (AAB-001) in patients with mild to moderate Alzheimer's disease. In the 18-month trial, bapineuzumab appeared to have clinical activity in treating Alzheimer's disease.
The study did not attain statistical significance on the primary efficacy endpoints in the overall study population. Post-hoc analyses did show statistically significant and clinically meaningful benefits in important subgroups.
In non-carriers of the Apolipoprotein E4 (ApoE4) allele, estimated in the literature to be from 40 to 70 per cent of the Alzheimer's disease population, post-hoc analyses showed statistically significant and clinically meaningful benefits associated with bapineuzumab treatment on several key efficacy endpoints, including the Alzheimer's Disease Assessment Scale (ADAS-cog), the Neuropsychological Test Battery (NTB), the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating - Sum of Boxes (CDR-SB). A favourable directional change was seen on the Disability Assessment Scale for Dementia (DAD), although this was not statistically significant.
Additionally in non-carriers, preliminary evaluation of MRI results showed less loss of brain volume among treated patients versus placebo patients, a finding that was statistically significant. Smaller increases in ventricular volume were seen in treated patients compared to placebo patients, although this finding was not statistically significant. Progression of Alzheimer's disease is generally associated with loss in brain volume and increases in ventricular volume. Further, treatment-related benefits seen on MRI were correlated to the favourable clinical changes observed in non-carriers.
In similar post-hoc analyses of carriers of the ApoE4 allele, no clinical benefits or statistically significant effects were observed on efficacy endpoints or the brain volume endpoint. However, favourable directional changes were observed on a number of endpoints. Preliminary analyses suggest possible increase of ventricular volume in treated patients versus placebo patients. The clinical significance of this finding is currently unclear and analyses are ongoing.
As expected given the nature of the population studied, adverse events were very common in both placebo and bapineuzumab-treated patients. In non-carriers, the number of patients experiencing serious adverse events was similar between placebo and bapineuzumab-treated patients. In carriers, serious adverse events were more frequently observed in bapineuzumab-treated patients than in placebo patients. In addition, vasogenic edema was reported in the treated population with an increased frequency in carriers and at higher doses. No cases were reported in placebo patients. In the ongoing phase III studies, carriers of the ApoE4 allele are being treated with a lower dose to minimize the risk of vasogenic edema. The Companies believe that the overall safety findings from this phase II trial support their prior decision to move to Phase 3 studies.
"The preliminary analyses of the phase II study are a continued validation of the amyloid approach to Alzheimer's disease and an important milestone in our companies' ongoing commitment to bring new treatment options to patients," said Kelly Martin, president and CEO of Elan. "These results clinically support our decision to move into phase III last year".
"We are encouraged by these findings. We remain driven by science and focused on patients as we work to bring this treatment to those who desperately need new options," said Bernard Poussot, president and CEO, Wyeth. "We recognize there is a great deal of hard work left as we move from this phase of learning towards confirming the potential of bapineuzumab".
Elan and Wyeth plan to continue all four studies in the previously disclosed bapineuzumab phase III clinical programme and will review and discuss these data with regulatory authorities and leading medical experts.
These findings reflect preliminary analyses of the phase II data and its implications for ongoing clinical development of bapineuzumab. In this trial, there were imbalances in patient numbers and characteristics at baseline between subgroups studied that may or may not have affected these results. Further analysis will continue in advance of a planned scientific presentation of detailed results of this study at the International Conference on Alzheimer's Disease (ICAD) in Chicago, July 29, 2008.
Bapineuzumab is the first humanized monoclonal antibody in late-stage investigation as a potential treatment for Alzheimer's disease. Bapineuzumab is designed to clear toxic beta amyloid from the brain. The beta amyloid protein is a key component of the neuritic plaques that are implicated in the pathology of Alzheimer's disease. A global phase III clinical programme was initiated in December 2007 and is intended to provide safety and efficacy data to support the filing and approval of licensing applications for bapineuzumab as a potential treatment for patients with mild to moderate Alzheimer's disease. To learn more about this enrollment, patients or caregivers should contact clinical sites directly. Participating clinical sites can be found by visiting www.icarastudy.com or, in the United States by calling 1 (888) 818-MEMORY. Study site details also can be found by visiting www.clinicaltrials.gov.
The Wyeth and Elan Alzheimer's Immunotherapy Program (AIP) includes investigational clinical programs for bapineuzumab. AIP is a collaboration between the two Companies to research, develop and commercialize immunotherapeutic approaches that may be used to treat and possibly prevent the onset of Alzheimer's disease. AIP research focuses on the beta amyloid hypothesis, as the Companies believe that enhancing the clearance of beta amyloid in the brain may provide a new treatment approach for Alzheimer's disease.