Anavex Life Sciences Corp (AVXL)

[Doc328]

The side effects of donepezil are mostly cholinergic (ACh having resuced breakdown via acetylcholinesterase inhibition) which affects gut motility. Donepezil is well tolerated by the majority of elderly patients when titrated from 5 to 10 mg after a month. That said, in my experience, 10-20 percent will stop its use because of tolerability. Those doing ok by 6 weeks usually continue to tolerate it well. A273 seems to have much better GI tolerability but more dizziness. Despite a statement "The were no TEAEs of clinical importance in the ANAVEX®2-73 (blarcamesine) cohort", more A273 patients dropped out of the PDD study due to AE's than placebo patients (and we don't have 30 mg vs 50 mg breakdown). 15.1% of A273 patients dropped out of the PDD study due to treatment emergent adverse events compared to only 7% of the placebo patients. A similar 5 of 32 patients dropped out of the small AD 2a by 31 weeks, despite many being on lower dose.


From A273 PDD presentation:

• Subjects with at least one TEAE leading to study discontinuation in the maintenance phase were 
 4.9% in the active cohort versus 4.7% receiving placebo 
 • The majority of TEAEs were observed during up-titration of which (light) dizziness (10.2% for active 
 drug versus 2.3% placebo) leading to study discontinuation while typical adverse effects seen in 
 marketed CNS drugs were not observed