Scientific programme

A03.e  Posters - Theme A - Beta-Amyloid Diseases
A03.e. Drug Development, Clinical Trials: Aggregation inhibitors

31-Mar-2017 08:00 18:00
 
 
Abstract: 103
TRAMIPROSATE EFFICACY IN APOE4 HOMOZYGOUS SUBJECTS WITH AD: LARGER EFFECTS IN MILD VERSUS MODERATE PATIENTS
Aims

OBJECTIVES

ALZ-801 is an oral pro-drug of tramiprosate being developed as a disease-modifying agent for Alzheimer’s disease (AD). Tramiprosate inhibits formation of Aβ oligomers and neurotoxicity. In a Phase 3 study in Mild/Moderate AD, tramiprosate did not demonstrate efficacy in the overall population but subgroup analyses showed promising signal in patients homozygous for e4 allele of apolipoprotein E (APOE4/4 homozygotes). Tramiprosate efficacy was further analyzed in APOE4/4 patients with Mild versus Moderate AD. 

Method

METHODS

The 78-week Phase 3 North American study enrolled 1,053 AD patients (MMSE range 16-26) on background of stable symptomatic AD drugs in 3 parallel arms: placebo, 100 mg BID, 150 mg BID. ADAS-cog and CDR-SB co-primary outcomes were analyzed using MMRM in Moderate (18-21) and Mild (22-26) subgroups.

Results

RESULTS

Analyses included 147 APOE4/4 homozygous AD patients. In the Mild AD subgroup (~65%), tramiprosate showed early and progressive trends for cognitive and functional benefit (nominally significant at Weeks 52-78). In the Moderate AD sub-group, early benefits were observed and sustained for 65 weeks (ADAS-cog) or 52 weeks (CDR-SB).Conclusion

CONCLUSIONS

In APOE4/4 AD population, tramiprosate showed largest benefit with sustained cognitive and functional improvement above baseline in Mild patients. This preferential efficacy in Mild AD is consistent with effects of other anti-amyloid agents. Surprisingly, Moderate AD patients also showed efficacy, lasting for ~65 weeks. This data suggests that ALZ-801, the optimized pro-drug of tramiprosate in preparation for Phase 3 studies, may provide benefit in both Mild and Moderate APOE4/4 patients, but with stronger effects in Mild patients.

 
Co-authors
S. Abushakra 1, J. Hey 2, A. Power 3, P. Wang 4, L. Shen 4, J. Hort 5, S. Gauthier 6, B. Vellas 7, A. Porsteinsson 8, M. Kivipelto 9, M. Tolar 10
1Alzheon- Inc., Chief Medical Officer, Framingham, USA
2Alzheon- Inc., CSO, Framingham, USA
3Alzheon- Inc., VP, Framingham, USA
4Pharmapace- Inc., Clinical, San Diego, USA
5Charles University, Scientific Advisory Board, Prague, Czech Republic
6McGill University, Scientific Advisory Board, Montreal, Canada
7University of Toulouse, Scientific Advisory Board, Toulouse, France
8University of Rochester, Scientific Advisory Board, Rochester, USA
9Karolinska University Hospital, Scientific Advisory Board, Stockholm, Sweden
10Alzheon- Inc., CEO, Framingham, USA