Scientific programme

S58  SYMPOSIUM
SYMPOSIUM 58 - LATE BREAKING THERAPEUTIC STRATEGIES IN AD AND PD

02-Apr-2017 11:45 13:45
 
 
Abstract:
PERSISTENT EFFICACY OF TRAMIPROSATE IN APOE4 HOMOZYGOUS AD SUBJECTS TREATED OVER 130 WEEKS: RESULTS OF NORTH AMERICAN EXTENSION STUDY
Aims

ALZ-801, oral pro-drug of tramiprosate, is in development as an Alzheimer’s disease (AD) treatment. Tramiprosate, the active molecule, is an amyloid anti-aggregation agent that inhibits formation of Aβ oligomers and neurotoxicity. In a Phase 3 study with tramiprosate, patients homozygous for the e4 allele of apolipoprotein E (APOE4/4 subgroup) showed significant efficacy over 78 weeks. Efficacy results for APOE4/4 patients who enrolled in extension study for an additional 52 weeks are presented.

Method

78-week Phase 3 North American study enrolled 1,053 AD patients (MMSE range 16-26) including 148 APOE4/4 homozygotes in 3 arms: placebo, 100mg BID, 150mg BID. Patients completing 78 weeks were offered extension study at the high dose. Drug assignment during the placebo-controlled phase remained blinded. Change from original baseline in ADAS-cog and CDR-SB were analyzed using MMRM at all visits up to 130 weeks.

Results

Total of 104 APOE4/4 homozygous patients enrolled in the extension study: 43, 33 and 28 from placebo, low and high-dose groups respectively; and 27, 25, 18 completed 130 weeks. The 150mg to 150mg group showed larger ADAS-cog benefits at both 104 and 130 weeks than the placebo to 150mg group (D = 3.9, p-value < 0.05), and a positive trend on CDR-SB (D = 1.0, p-value < 0.1). Adverse event profile was favorable, similar to blinded phase.

Conclusion

APOE4/4 AD patients tramiprosate exhibited sustained cognitive and functional benefits over 2.5 years, compared to patients whose treatment was delayed by 78 weeks (delayed start group). Efficacy profile supports a disease-modifying benefit, consistent with amyloid anti-aggregation action.

 
Co-authors
S. Abushakra 1, P. Scheltens 2, C. Sadowsky 3, A. Power 4, S. Gauthier 5, B. Vellas 6, A. Porsteinsson 7, P. Wang 8, L. Shen 9, J. Hey 10, M. Tolar 11
1Alzheon- Inc., Chief Medical Officer, Framingham, USA
2VU University Medical Center, Hoofd Alzheimercentrum, Amsterdam, The Netherlands
3Palm Beach Neurology, Medical Director, West Palm Beach- Florida, USA
4Alzheon- Inc., VP Program Development, Framingham, USA
5McGill University, Director- Alzheimer Disease Research Unit, Montreal, Canada
6University of Toulouse, Professor of Medicine and Chairman of the Department of Internal and Geriatric Medicine, Toulouse, France
7University of Rochester, Professor of Psychiatry and Director Memory Disorders Clinic, Rochester, USA
8Pharmapace- Inc., Director, San Diego, USA
9Pharmapace- Inc., President & CEO, San Diego, USA
10Alzheon- Inc., Chief Scientific Officer, Framingham, USA
11Alzheon- Inc., President & CEO, Framingham, USA