Date: 2013-01-31
Type of information: Halting of the trial
phase: 2
Announcement: discontinuation of development
Company: AC Immune (Switzerland)
Product: ACI-91
Action
mechanism: ACI-91 (pirenzepine) is a muscarinic acetylcholine inhibitor which indirectly down-regulates the expression and activity of the beta-secretase BACE-1 in pre-clinical studies. BACE-1 is regarded as a key target for therapies treating Alzheimer\'s disease. Evidence suggests that inhibiting BACE-1 decreases the production of the Abeta peptide and therefore may reduce amyloid plaque formation which is associated with the disease.
The drug was in-licensed. It is approved in a number of European countries for the treatment of stomach and intestinal ulcers.
Disease: Alzheimer's disease
Therapeutic area: Neurodegenerative diseases
Country: Germany, Austria
Trial
details: The primary objective was to assess safety and tolerability including examination for potential negative effects on cognition during 12 months treatment with ACI-91 compared to placebo. Secondary objectives included assessing the biochemical effects of ACI-91 on biomarkers of Alzheimer\'s disease such as BACE-1, Abeta and total Tau and to explore the effects of ACI-91 on cognition, global function, activities of daily living and neuropsychiatric symptoms.
The Phase II trial enrolled 63 patients with mild to moderate Alzheimer\'s disease in 16 centers across Germany and Austria. They were treated with oral doses of 75 mg of ACI-91 or placebo twice a day (total daily dose 150 mg) for 12 months, on top of standard therapy of an acetylcholinesterase inhibitor.
Latest
news: AC Immune has announced that it has stopped development of the small molecular entity ACI-91. This follows results of a Phase II trial in 63 patients with mild to moderate Alzheimer\'s disease. The Phase II clinical study was based on intriguing pre-clinical data which suggested that ACI-91 eliminates the Abeta peptide from the brain and improves cognition. Based on these results and the known peripheral effects outside the brain for short-term use of ACI-91, it was decided to conduct a limited Phase II study in Alzheimer\'s patients to evaluate the safety of long-term administration of the drug.
Although the overall tolerability of ACI-91 was rated as good in most patients, it was associated with a general, but statistically not significant, decrease of measures of cognitive performance and clinical function. There were also no consistent effects on biomarkers of the disease.
It is presumed that the negative effect on cognition is likely to be related to ACI-91\'s unexpected central anticholinergic properties, to which the study population may have been relatively susceptible. Consequently any potential positive peripheral effect of ACI-91, as shown in the pre-clinical studies, was not strong enough to outweigh these anticholinergic properties.
