CAD106, ALZT-OP1, BAN2401, and AVANEX 2073. These words may sound like the names of droids or spaceships in a Star Wars movie, but these acronyms and titles are worth getting to know as they represent new clinical phase 3 trials for Alzheimer’s disease that are actively enrolling patients.
The current Alzheimer’s disease drug pipeline was reviewed in the journal CELL by Cure Alzheimer’s Fund Research Leadership Group member Dr. David Holtzman. In this review article, Dr. Holtzman weighs in on the basic science insights that are informing the next generation of clinical trials. Although the therapeutic pipeline for Alzheimer’s disease has seen its share of challenges and adversity, and several pharmaceutical companies have abandoned their Alzheimer’s disease drug development division, there are still novel, therapeutic strategies that are actively being developed for Alzheimer’s disease.
Currently, four FDA-approved medications for the management of cognitive impairment for individuals with Alzheimer’s disease are available. These include:
The first three belong to the same class of drugs called cholinesterase inhibitors. These drugs prevent the breakdown of acetylcholine, a neurotransmitter messenger important for learning and memory. Communication between nerve cells can be supported by keeping acetylcholine levels high. Memantine is administered in later stages of Alzheimer’s when the disease is more severe. This drug regulates the activity of glutamate, a chemical that is involved in processing information, memory storage, and retrieval. These treatment strategies are designed to manage symptoms and are limited in their capacity to slow the progression of neurodegeneration.
As reported by Dr. Holtzman more than 20 compounds have completed large, phase 3 clinical trials in groups of patients with various stages of Alzheimer’s disease. All have failed to delay cognitive impairment and memory loss. Often these drug trials were administered to patients who already had Alzheimer’s symptoms. While mild to moderate symptoms of Alzheimer’s disease may sound like only an intermediate phase in terms of the clinical progression of the disease, in terms of the biology, this actually represents a very advanced stage of the disease.
The plaques and tangles associated with Alzheimer’s begin to accumulate 15-20 years before the onset of symptoms. Significant cell death and irreversible synaptic dysfunction may have already occurred rendering the drugs ineffective. It is for this reason that many drugs for Alzheimer’s disease have failed in clinical trials. To tackle the disease effectively, disease-modifying clinical interventions will need to be administered in pre-clinical stages – before symptoms have emerged.
Seven new drugs are set to begin phase 3 clinical trials. These drugs will be administered to patients who are in the earliest stages of Alzheimer’s disease, or who are cognitively normal but carry two copies of a gene called ApoE4 that puts them at increased risk for developing Alzheimer’s.
This list does not include the multitude of compounds that are currently in Phase 1 and Phase 2 clinical trials. For a description of the various clinical trial stages, please visit the National Institute of Aging website: https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies#four.