According to the Alzheimer’s association, in 2022 approximately 6.5 million Americans are living with Alzheimer’s disease. Many clinical trials are now focusing on key therapeutics that can help limit the disease progression of Alzheimer’s. This week, it was reported that Roche’s therapeutic gantenerumab failed to slow Alzheimer’s progression and restrict memory loss for those who were in an early phase of the disease. The two trials, which were in Phase III, failed to meet primary endpoints and the level of beta-amyloid reduction was lower than expected. According to GlobalData’s clinical trial database, the drug candidate is a fully human monoclonal antibody that acts by targeting amyloid-beta peptide (an amyloid precursor protein). It is developed based on human combinatorial antibody library (HuCAL) fab technology.
Gantenerumab is an amyloid beta peptide inhibitor. Beta amyloid is a protein fragment snipped from an amyloid precursor protein; in a healthy brain, these protein fragments are broken down and eliminated, but the accumulation of beta-amyloid in neuritic plaques is thought to be causative for the progression of Alzheimer’s disease. Gantenerumab inhibits cerebral beta amyloid peptide formation, with the intention of treating Alzheimer’s disease.
Additionally, according to the database, there are 23 trials listed for Roche investigating gantenerumab. 15 of these trials have been completed, seven are ongoing, and one is currently planned. When looking at the wider trial landscape for Alzheimer’s trials, donepezil hydrochloride seems to be the leading primary intervention for Alzheimer’s, with a total of 75 clinical trials. A popular marketed treatment for Alzheimer’s, the drug works by being a reversible inhibitor of acetylcholinesterase (AChE), the predominant cholinesterase in the brain. By inhibiting the hydrolysis of acetylcholine by AChE, donepezil increases acetylcholine concentrations, enhancing cholinergic function. This increases the amount of acetylcholine in synapses and potentially enhances the brain cholinergic neurotransmission.
Research within the field of Alzheimer’s has been increasingly competitive. Recently, Biogen and Eisai’s drug candidate, lecanemab, showed positive results within trials. Lecanemab, also a beta amyloid reducing drug, slowed the decline of brain function in Alzheimer’s disease by approximately 27%, compared with a placebo. With research activity being extremely active in this area, it is expected that suitable therapeutics will soon be proven effective.
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