Responder Analyses from a 78-Week Phase 2 Placebo-Controlled Study of ELND005 (Scyllo-Inositol) in Mild to Moderate (MM) Alzheimer's Disease (AD) (P04.195)

Abstract

Objective: To evaluate responder proportions in Mild AD using new responder criteria, to inform selection of optimal definitions in future studies of this candidate oral disease modifying agent. Background This study enrolled 353 M/M patients (MMSE 16-26) to placebo or ELND005 (250mg, 1000mg, or 2000mg, all BID). Safety findings led to discontinuation of the 2 highest doses, efficacy analyses were based on placebo and 250mg arms. Treatment effects were not significant in M/M population for NTB, ADCS-ADL (cognitive, functional co-primary outcomes). In pre-specified Mild AD analyses, NTB showed significant effects in study completers (Salloway et al., Neurology 2011). The CDR-SB will likely be the co-primary global outcome in future studies, thus responder analyses focused on NTB and CDR-SB. Design/Methods: Responder definitions explored in m-ITT population were: 1. NTB responders: NTB change from baseline ≥ 0; 2. CDR-SB responder: CDR-SB ≤ 0; 3. Response on either NTB or CDR-SB. Responder proportions were analyzed in M/M and Mild group (MMSE 22-26), with no adjustments for multiplicity testing. Results: In M/M group, there were 15.7 and 32.7% NTB responders (N=51/52, p= 0.07), NTB or CDR responders were 23.5 and 38.5% in placebo/250mg groups (NS); while in Mild group, there were 15.6% and 50.0% NTB responders (N=32/32, p or CDR responders were 25.0% and 56.3% (p= 0.02) in placebo/250mg groups. In both M/M and Mild groups CDR-SB responder proportions to ELND005 were small (15.4%, 21.9%) and differences from placebo (13.7%, 18.8%) were NS. Conclusions: Responder proportions with ELND005 were consistently higher in Mild than in M/M AD. Using the “either NTB or CDR-SB” responder definition, responsder proportion was significantly higher on ELND005 than placebo in Mild patients, where 56% improved or remained stable at week 78. These responder analyses support the positive NTB trends in pre-specified analyses of Mild AD, and will be included in future studies. Supported by: Elan Pharmaceuticals, South San Francisco, CA. Disclosure: 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. 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. 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. 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.