Responders to ELND005 (Scyllo-Inositol) Demonstrate Clinical and Biomarker Characteristics Consistent with Mild Alzheimer's Disease (AD): Data from a 78-Week Phase 2 Study in Mild to Moderate (M/M) AD (P04.194)

Abstract

Objective: To describe the clinical and biomarker characteristics (v-MRI and CSF) of patients who demonstrated cognitive benefit on ELND005, a candidate disease modifying agent. Background Post-hoc analyses were from a Phase 2, placebo-controlled, 78 week study in 353 M/M AD patients (MMSE 16-26), which included 3 active arms (250, 1000 and 2000mg all BID). The 2 highest doses were discontinued due to safety findings (Salloway et al. Neurology 2011). Design/Methods: Clinical response was defined as improved or stable Neuropsychological Test Battery scores (NTB, co-primary outcome) assessed in all 3 doses at 78 weeks. Baseline parameters and percent changes from baseline were compared using t-tests. Correlation analyses were performed on response rate, defined as number of times a patient9s NTB remained ≥0 at any visit divided by time on study. Results: Clinical responders compared to non-responders (n= 39/109), had significantly higher baseline MMSE (mean 23.3 versus 20.6, p Conclusions: Patients who improved or remained stable at 78 weeks had mild disease at baseline, by MMSE and CSF tau pararmeters. Clinical responders developed significantly less brain atrophy and ventricular enlargement than non-responders over 78 weeks. Correlations of CSF biomarkers and clinical outcome changes were limited by the small CSF sample size at study endpoint (N=34). These data support the potential benefit of ELND005 when treatment is initiated at the Mild AD stage, and help define the population for future studies. Supported by: Elan Pharmaceuticals, South San Francisco, CA. Disclosure: Dr. Porsteinsson has received personal compensation for activities with Medivation, Elan, Janssen Immunotherapy, Pfizer, Transition Therapeutics, and Forest LaboratoriesDr Porsteinsson has received research support from BMS, Baxter, Elan, Janssen Immunotherapy, Medivation, Pfizer, Toyama, and Wyeth. Dr. Sperling has received personal compensation for activities with Pfizer Inc, Bristol-Myers Squibb, Janssen, and Elan as a consultant. Dr. Sperling has received research support from Bristol-Myers Squibb and Elan. Dr. Salloway has received personal compensation for activities with Elan Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Pfizer Inc, Eisai Inc., Bristol-Myers Squibb, Novartis, Forest, and Athena Diagnostics. Dr. Salloway has received research support from Eisai Inc., Pfizer Inc, Forest Laboratories, Inc., Janssen Pharmaceutica, Medivation, GlaxoSmithKline, Inc., Myriad Pharmaceuticals, Elan Corporation, Neurochem, Wyeth, Bristol-Myers Squibb, Voyager, and Cephalon, Inc. Dr. Crans has received personal compensation for activities with Elan Pharmaceuticals and JANSSEN Alzheimer Immunotherapy Research and Development, LLC. Dr. Hernandez has received personal compensation for activities with Elan Pharmaceuticals as an employee. Dr. Abu-Shakra has receievd personal compensation for activities with Allergan, Inc as an employee.