Yet another failed late-stage trial in Alzheimer’s disease

Alzheimer’s disease has proven a very difficult area for drug development. In the last decade many drugs have failed in late-stage clinical trials and Axovant’s 5-hydroxytryptamine (5-HT) 6 receptor antagonist, intepirdine, faced the same misfortune earlier this week. The company reported their Phase 3 MINDSET trial in patients with mild to moderate Alzheimer’s disease failed to meet co-primary endpoints. Similar molecules developed by Pfizer and Lundbeck also failed late stage trials recently, generating concern with this class of drugs.

5-HT6 receptor antagonists are small molecules which function by targeting a range of receptors for cholinergic enhancement and symptom reducing effects. This is based on the cholinergic hypothesis for Alzheimer’s disease (i.e., dysfunction of acetylcholine containing neurons contributes to cognitive decline). Other major classes of Alzheimer’s drugs in development are based on the amyloid cascade hypothesis. Vaccines and other immunotherapies are also being investigated to prevent progression of the disease.

Although this is a challenging area of development, there are currently numerous molecules in the pipeline for Alzheimer’s disease with almost 30 agents in Phase III trials. Trials begin reporting in 2019 with hopefully positive news for Alzheimer’s patients.