Drug Development and Pipeline Analysis in the Alzheimer’s Disease Market Space

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is a lead cause of dementia in approximately 5.8 million Americans. Further, it is estimated that the number will soar to 13.5 million by 2050. 

Owing to the R&D done in understanding Alzheimer’s disease so far, it has been clear that there is an abnormally massive build-up of protein fragment beta-amyloid (called beta-amyloid plaques) outside neurons and tau protein (called tau tangles) inside neurons, which are a core reason behind the inference between neuron-to-neuron communication at synapses and blocking of the transportation of nutrients and other essential molecules inside the neuron. When the disease is still in its initial stages, the brain tries to compensate for the lost neurons, however, as the disease advances at a rapid pace, the brain fails in its coup, and several different symptoms such as loss of cognition, memory lapse, changes in personalities and moods, confusion and others begin to appear. 

Yet, there is no proper diagnosing test for dementia and physicians assess the condition on the basis of family history and symptoms. There is a need for biomarkers that can help indicate the presence of risk and progression of the disease. Further, none of the pharmacologic treatments is available directed to slow or stop the damage caused due to Alzheimer’s disease. The approved USFDA medication include cholinesterase inhibitors (Aricept, Exelon, Razadyne) and memantine (Namenda). These drugs help by improving symptoms by increasing the number of neurotransmitters in the brain, however, memantine blocks receptors in the brain from excess stimulation that can damage nerve cells. 

However, many researchers are working to develop treatments and advance the Alzheimer’s disease pipeline that can slow or stop the progression of Alzheimer’s disease as well as preserve the function of the brain. Several key players such as Eisai, BioArctic AB, Biogen, Hoffmann-La Roche/Chugai Pharmaceuticals, Anavex Life Sciences Corp., Neurimmune, Neurotrope, vTv Therapeutics, AgeneBio, AZTherapies, Otsuka, Novartis/ Amgen, Roche, Cerecin, AbbVie, Araclon biotech, Genentech, Lundbeck, and others are actively working in the space to bring novel therapies in the Alzheimer’s disease market. 

Lecanemab (BAN2401), a humanized, monoclonal, anti-Aβ soluble aggregate (protofibril) antibody is under Phase III clinical study Clarity by Eisai and Biogen. Biogen is also investigating Aducanumab (BIIB037), which is a human monoclonal antibody for the treatment of Alzheimer’s disease. The company has already submitted the Biologics License Applications (BLA) application and has received a priority review designation from the US FDA.

ALZT-OP1 is also in the phase III clinical stage of development for Early Alzheimer’s Disease by AZ Therapies. It is a first-in-class candidate to slow the progression of Alzheimer’s disease and is a combination of two previously approved small molecules re-engineered to provide a daily dose to suppress the brain’s neuroinflammatory response. 

Another phase III candidate is Cerecin’s investigational product, Tricaprilin, a highly purified proprietary, oral formulation of a medium-chain triglyceride. It is being investigated in subjects with mild to moderately severe probable Alzheimer’s disease and who are non-carriers of the APOE4 Allele. An investigational phase III immunotherapy Gantenerumab (RG1450, RO4909832) is under trials to treat Alzheimer’s disease by potentially reducing beta-amyloid plaques in the brain. The therapy is being developed by Chugai Pharmaceuticals (now part of Hoffmann-La Roche). 

Another therapy in the Alzheimer’s disease pipeline that has shown promise in slowing down the disease progression under phase II trials of development by Alector, is AL002, an investigational, humanized monoclonal antibody. Alector is running the trials in collaboration with AbbVie. Reviva Pharmaceuticals’s Brilaroxazine (RP5063), is running trials of the therapy in multiple clinical trials including Alzheimer’s disease.  

With the increasing prevalence of Alzheimer’s disease and the rising geriatric population, there is a demand for better treatments and great attention towards neurodegenerative disorders. At present, there is no disease-modifying therapy in the Alzheimer’s disease market. The ongoing research to better understand disease pathophysiology and identification of biomarkers will help early detection of the condition, thereby, augmenting the therapy development process. 

With trials of several tau‐targeting monoclonal antibodies, monoclonal antibodies targeting prefibrillar amyloid, removing fibrillar amyloid-beta (Aß) and others, the Alzheimer’s disease pipeline landscape appears quite fulfilling and rich. Along with novel therapies, several trials are repurposing drugs. 

The discovery of the fact that the symptoms of Alzheimer’s disease take about 20 years or so to appear gives leeway to intervene and prevent serious brain damage due to the condition. With several therapies in the AD pipeline and bolstered expenditure in the R&D of neurodegenerative disorders, it is possible to find a cure and break the Alzheimer’s disease continuum.