by Alzheimer’s disease is one of the biggest health challenges facing the world today as the population ages. This progressive brain disorder slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. As of now, there is no cure for Alzheimer’s, but significant progress has been made in developing drugs to treat symptoms and slow the progression of the disease. Here is an overview of the current FDA-approved drugs along with some promising drugs in the pipeline.
FDA-Approved Drugs for Symptom Management
There are five drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease. All of these drugs target the deficiency of a chemical messenger called acetylcholine in the brain.
Donepezil (Aricept): Donepezil was the first FDA-approved drug for Alzheimer’s treatment in 1996. It is a cholinesterase inhibitor that prevents the breakdown of acetylcholine in the brain, thereby increasing its levels. Donepezil can provide modest improvements in cognition, functioning, and behaviour for mild to moderate cases of Alzheimer’s. Common side effects include nausea, vomiting, diarrhea, muscle cramps and fatigue.
Rivastigmine (Exelon): Approved in 2000, Rivastigmine is also a cholinesterase inhibitor that works in a similar manner as Donepezil. It too can provide symptomatic benefits for mild to moderate Alzheimer’s cases. Side effects are also comparable and include nausea, vomiting, diarrhea, fatigue, and muscle weakness.
Galantamine (Razadyne): Another cholinesterase inhibitor, Galantamine received FDA approval in 2001. It is also effective in mildly to moderately affected Alzheimer’s patients by boosting acetylcholine. Common side effects include nausea, vomiting, diarrhea, dizziness and fatigue.
Memantine (Namenda): This drug has a different mechanism of action compared to cholinesterase inhibitors. Memantine is an NMDA receptor antagonist that regulates glutamate activity and provides benefits for moderate to severe Alzheimer’s cases. Namenda was approved in 2003 and can help improve cognition, performance of daily activities, and behavior. Side effects include dizziness, headache and confusion.
Rivastigmine patch (Exelon Patch): The rivastigmine transdermal patch was approved in 2006 and delivers rivastigmine through the skin for around 24 hours, avoiding gastrointestinal side effects seen with oral administration. It can benefit mild to moderate cases.
While these drugs don’t cure or alter the progression of Alzheimer’s Drug they can provide symptomatic relief for a temporary period by managing memory issues, thinking ability, mood, and behavior challenges. However, their effectiveness reduces over time as the disease progresses. Newer and more effective treatment options are thus needed.
Emerging Therapies Targeting Amyloid Plaques
A hallmark feature of Alzheimer’s is the accumulation of amyloid beta protein plaques in the brain. Several investigational drugs in clinical trials are designed to target these plaques.
Aducanumab (Biogen): Aducanumab is a monoclonal antibody that targets aggregated forms of amyloid beta. In early-stage trials, it showed signs of reducing plaques and slowing clinical decline. However, a Phase 3 trial was discontinued in 2019 as preliminary analysis showed it was unlikely to meet the primary endpoint. Biogen plans to refile for FDA approval.
Lecanemab (Eisai & Biogen): This antibody binds to aggregated forms of amyloid beta to target plaques. Initial Phase 2 trial data showed plaque reduction of over 50% compared to placebo. Phase 3 clinical efficacy studies are ongoing. Results are expected in 2022.
Donanemab (Eli Lilly): This antibody targets forms of amyloid beta preceding plaque formation. Early-stage trial results showed plaque and tau reduction. A Phase 2 secondary prevention study in asymptomatic patients is currently underway.
BAN2401 (Eisai): An anti-amyloid beta protofibril antibody, BAN2401 demonstrated plaque reduction and slowed decline on cognitive tests in Phase 2 trials. Phase 3 clinical efficacy studies began in 2020 with results expected in 2022-23.
If successful in late-stage trials, these amyloid-targeting drugs have the potential to become the first disease-modifying therapies for Alzheimer’s by slowing or stopping cognitive decline. However, there are still no guarantees, and many challenges remain, including early identification of patients and determining the right time window for treatment. Researchers are hopeful that ongoing and future clinical research will provide answers.
Exploring Other Therapeutic Targets
Apart from amyloid plaques, other Alzheimer’s pathology hallmarks like neurofibrillary tangles and neuroinflammation are also being pursued as treatment targets:
Tau antibodies targeting abnormal tau protein tangles such as Roche’s gosuranemab and Biogen’s BIIB080 are in Phase 2 trials.
Anti-neuroinflammatory drugs such as Pfizer’s PFE-5482 targeting microglial neuroinflammation are in early-stage trials.
Other investigational approaches include drugs targeting neurotransmitter systems, cerebral spinal fluid circulation, metabolic changes, and neuroprotection/regeneration pathways.
While still very much in experimental stages, such multi-pronged strategies hold promise in developing disease-modifying treatments targeting multiple aspects of Alzheimer’s pathology simultaneously for greater efficacy. Researchers emphasize the need for early testing of combinations as well. Continuous funding and accelerating clinical research will be crucial to realize this potential.
Concluding Thoughts
In summary, researchers have made important progress in developing drugs for Alzheimer’s disease symptom management as well as more innovative disease-modifying candidates. While curative treatment remains elusive for now, emerging therapies targeting amyloid plaques and other underlying causes offer hope. If pivotal trials succeed, the first true disease-altering drugs could become available in the near future. However, much work still needs to be done. With aging populations, Alzheimer’s poses one of the biggest healthcare challenges globally. Sustained scientific commitment will be essential to eventually find effective means of prevention, treatment and care.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
