Alzheimer's disease (AD) drug development has faced significant challenges, with few candidates advancing through clinical trials. The study analyzed clinical trials from 2002 to 2012, revealing that only 0.4% of compounds progressed to regulatory review, indicating a high attrition rate. A total of 413 trials were conducted, with 78% sponsored by the pharmaceutical industry. The majority of trials focused on symptomatic agents aimed at improving cognition (36.6%) and disease-modifying small molecules (35.1%). Trials for disease-modifying agents were longer and involved more participants than those for symptomatic agents. The success rate for advancing from one phase to the next was low, with 21% of Phase 1 compounds advancing to Phase 2 and 8% advancing from Phase 2 to Phase 3. Only one compound, memantine, was approved for marketing during the study period. The current AD drug development pipeline includes 110 trials, with 22 unique therapies in Phase 1, 49 in Phase 2, and 23 in Phase 3. Despite the high failure rate, research continues to focus on disease-modifying agents targeting amyloid-beta protein, though none have shown efficacy in clinical trials. The study highlights the need for improved trial design, better patient selection, and more effective drug development strategies to increase the success rate of AD therapies. The AD drug development ecosystem requires support to address the growing burden of the disease.Alzheimer's disease (AD) drug development has faced significant challenges, with few candidates advancing through clinical trials. The study analyzed clinical trials from 2002 to 2012, revealing that only 0.4% of compounds progressed to regulatory review, indicating a high attrition rate. A total of 413 trials were conducted, with 78% sponsored by the pharmaceutical industry. The majority of trials focused on symptomatic agents aimed at improving cognition (36.6%) and disease-modifying small molecules (35.1%). Trials for disease-modifying agents were longer and involved more participants than those for symptomatic agents. The success rate for advancing from one phase to the next was low, with 21% of Phase 1 compounds advancing to Phase 2 and 8% advancing from Phase 2 to Phase 3. Only one compound, memantine, was approved for marketing during the study period. The current AD drug development pipeline includes 110 trials, with 22 unique therapies in Phase 1, 49 in Phase 2, and 23 in Phase 3. Despite the high failure rate, research continues to focus on disease-modifying agents targeting amyloid-beta protein, though none have shown efficacy in clinical trials. The study highlights the need for improved trial design, better patient selection, and more effective drug development strategies to increase the success rate of AD therapies. The AD drug development ecosystem requires support to address the growing burden of the disease.