AN1792 Long-Term Follow-Up Published and Available Online
Results add to body of knowledge underlying Elan-Wyeth Alzheimer’s Immunotherapy Program
A paper regarding the initial candidate of Elan and Wyeth’s Alzheimer’s Immunotherapy Program has been published in Current Alzheimer Research and is available online. The publication titled “Long-Term Follow-Up of Patients Immunized with AN1792: Reduced Functional Decline in Antibody Responders” describes the results of a study whose findings were first presented at key scientific conferences in mid-2007.
While the long-term follow-up data assessed in the study (referred to as AN1792-251 or Study 251), is limited and must be interpreted cautiously, Elan believes the study’s conclusions are supportive of the hypotheses underpinning the basic premises of beta amyloid immunotherapy. Central to these is the “beta amyloid cascade”: the process by which beta amyloid is generated, aggregates and is ultimately deposited in the brain as plaques. The formation of beta amyloid plaques is a hallmark pathology of Alzheimer’s disease.
Efficacy Assessment after Four-and-a-half Years
Study 251 was a follow-up assessment of a subset (approximately 40%) of participants in AN1792-Study 201, a Phase 2 clinical study comprising 372 patients with mild to moderate Alzheimer’s disease that tested AN1792, a synthetic beta amyloid peptide prepared for use in immunizing patients against beta amyloid. The Phase 2 study was discontinued in 2002 when six percent of patients developed meningoencephalitis. Study 201 Investigators contacted patients to assess their willingness to participate in the follow-up assessments.
The Study 251 assessments occurred 4-5 years after patients were immunized with AN1792 and showed positive indications of a clinical effect in a subset of patients identified as “responders” to AN1792, meaning they had produced a detectable antibody response to the immunization.
The study evaluated changes in functional, dependence, and global measures on a number of scales, including the Disability Assessment for Dementia (DAD) scale, the Dependence Scale (a measurement of caregiver dependence), the Clinical Dimension Ratio Sum of Boxes (CDR-SOB) scale, the Neuropsychological Test Battery (NTB), the Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale (ADAS-cog).
Compared with placebo, there were favorable trends for responders versus placebo on the DAD, Dependence Scale and CDR-SOB scale, although the difference on the latter was not statistically significant.
No significant differences were observed in the change from baseline for the overall NTB 9-component z-score between antibody responders and placebo-treated patients, although there were favorable trends on some cognitive NTB subsets. No significant differences were observed between responders and placebo-treated patients on the MMSE and ADAS-cog instruments.
AN1792, Study 251 and Bapineuzumab
Elan’s Alzheimer’s Immunotherapy Program Team Leader Jeannie Giacchino, MD, PhD, noted that both AN1792 and Study 251 were key parts of the immunotherapy body of work that helped shape the bapineuzumab clinical program. Dr. Giacchino said, “We believe this work supports the hypothesis that beta amyloid immunotherapy may have long-term functional benefits. This study is part of the totality of the data, across the Elan-Wyeth Alliance, that informs our strategic decisions relative to our Alzheimer’s Immunotherapy Program.”