by Alzheimer’s disease is a debilitating neurodegenerative disorder that causes progressive memory loss, impairment of thinking abilities and behavioral changes. Currently available drugs can only provide modest and temporary improvements in symptoms but cannot stop or reverse the underlying progression of the disease. However, recent years have seen significant developments in research towards disease-modifying therapies that may slow or halt cognitive decline in Alzheimer’s patients. Here are some key updates on promising new drugs in clinical trials for Alzheimer’s disease.
Anti-amyloid Beta Drugs
One of the hallmarks of Alzheimer’s pathology is the accumulation of amyloid beta protein plaques in the brain. Several drugs have been developed to target these amyloid plaques by blocking amyloid beta production or enhancing its clearance from the brain. Among these, antibodies targeting amyloid beta have generated significant interest.
Aducanumab is a human monoclonal antibody that targets soluble amyloid beta. In late stage clinical trials, it showed a significant dose-dependent reduction of amyloid beta plaques and slowing of clinical decline in early Alzheimer’s patients. Based on these promising results, the drug received accelerated approval from FDA in 2021 for the treatment of Alzheimer’s. However, its efficacy is still being evaluated in continuation trials due to some conflicting data.
Another amyloid beta antibody, Lecanemab, showed reduced amyloid burden and slowed clinical progression in a phase 2 clinical trial. Its phase 3 study is currently ongoing to confirm these initial findings. Other anti-amyloid antibodies like Gantenerumab and BAN2401 are also in late phase trials, with results expected in the coming years. If proven effective, these drugs may fundamentally change Alzheimer’s treatment paradigms.
Anti-tau Drugs
Accumulation and aggregation of abnormal tau protein is another key Alzheimer’s pathology. Several drugs targeting tau are now in various stages of clinical development.
One such candidate is Semorinemab, a humanized monoclonal antibody that targets tau tangles. Its phase 2 clinical trial showed reduced tau accumulation in the brain and stabilization of cognition compared to placebo in early Alzheimer’s patients. Phase 3 studies are ongoing to validate these results.
Another promising tau-directed drug is Zvilipidem, an orally administered drug that inhibits tau aggregation. Its phase 2 trial showed a trend towards slower clinical and biomarker progression in participants with prodromal to mild Alzheimer’s disease. Larger phase 3 efficacy studies are planned.
Other anti-tau drugs like AVP-1571, BIIB092 and E2814 are also advancing through clinical trials, aiming to halt tau-mediated neurodegeneration in Alzheimer’s and related tauopathies like frontotemporal dementia.
Multi-target Drugs
While most disease-modifying trials focus on targeting a single amyloid or tau pathology, some next generation drugs aim at multiple Alzheimer’s Drug targets simultaneously. For example, CNP520 is an orally active drug with mixed mechanisms targeting both amyloid beta and tau pathologies. Its phase 2 trial results demonstrated reduced amyloid and tau levels with associated cognitive benefits compared to placebo.
Another multi-target drug is UCB0107 which inhibits amyloid beta production while enhancing its clearance. It also hampers tau aggregation and propagation between neurons. Results from ongoing phase 2 and 3 trials of UCB0107 are eagerly awaited next year. These multi-target drugs, if successful, could provide more comprehensive treatment against Alzheimer’s heterogeneous pathologies.
Pipeline of Other Novel Mechanisms
In addition to amyloid and tau drugs, novel mechanisms are also being explored in early stage trials. For example, treatments enhancing cerebral blood flow like SMARCB1 gene therapy may improve neuronal metabolism and function in Alzheimer’s. Neuroinflammation modulators like anakinra are being tested for their disease-modifying potential. Drugs repurposing failed anti-diabetic drug traxxamed for neuroprotection completed early trials with promising safety.
Several lifestyle interventions like diet, exercise and cognitive training are also being combined with drug therapies in clinical trials. Interestingly, respiratory chain enzyme enhancers under investigation may leverage the links between mitochondrial dysfunction and neurodegeneration in Alzheimer’s disease. With diverse avenues being actively pursued, an effective disease-modifying therapy seems within reach in the next 5-10 years.
Challenges Remain
While major advances are quickly unfolding in Alzheimer’s drug development, significant challenges remain. Key among them are identifying patients at early symptomatic or even pre-symptomatic stages. Initiating treatment much before extensive neuron loss occurs seems critical for success. Biomarker-based enrollment strategies are being optimized to detect individuals likely to progress rapidly versus slowly and inform trial designs.
Ensuring consistent trial methodologies and outcomes assessment across global multi-center studies continues posing difficulties. Selection of appropriate cognitive and functional endpoints sensitive to subtle drug effects over 1-2 year periods remains complex. Powering trials adequately with sample sizes in thousands also significantly increases costs. Despite challenges, unprecedented industry investments and accelerated regulatory initiatives are bringing hope of conquering this devastating condition before the end of this decade. These are definitely exciting times in Alzheimer’s therapeutics research.
Current clinical progress validates decades of scientific advances in understanding Alzheimer’s mechanisms and holds promise for establishing effective disease-modifying therapies in the near future. Continued investments in multi-disciplinary research across diverse academic and industrial partnerships will help overcome existing challenges and ultimately defeat this debilitating brain disorder. With several game-changing drugs in late stages, a breakthrough seems within reach for the over 50 million Alzheimer’s patients worldwide.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
