Alzheimer’s disease drug-development pipeline: few candidates, frequent failures

By Jeffrey L. Cummings, Travis Morstorf, K. Zhong. Alzheimer's Research & Therapy, 2014

1,640 citations recorded by the source corpus.

Alzheimer’s disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD. We examined Clinicaltrials.gov, a public website that records ongoing clinical trials. We examined the decade of 2002 to 2012, to better understand AD-drug development. We reviewed trials by sponsor, sites, drug mechanism of action, duration, number of patients required, and rate of success in terms of advancement from one phase to the next. We also reviewed the current AD therapy pipeline. During the 2002 to 2012 observation period, 413 AD trials were performed: 124 Phase 1 trials, 206 Phase 2 trials, and 83 Phase 3 trials. Seventy-eight percent were sponsored by pharmaceutical companies. The United States of America (U.S.) remains the single world region with the greatest number of trials; cumulatively, more non-U.S. than U.S. trials are performed. The largest number of registered trials addressed symptomatic agents aimed at improving cognition (36.6%), followed by trials of disease-modifying small molecules (35.1%) and trials of disease-modifying immunotherapies (18%). The mean length of trials increases from Phase 2 to Phase 3, and the number of participants in trials increases between Phase 2 and Phase 3. Trials of disease-modifying agents are larger and longer than those for symptomatic agents. A very high attrition rate was found, with an overall success rate during the 2002 to 2012 period of 0.4% (99.6% failure). The Clinicaltrials.gov database demonstrates that relatively few clinical trials are undertaken for AD therapeutics, considering the magnitude of the problem. The success rate for advancing from one phase to another is low, and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. The AD drug-development ecosystem requires support.

Subfields: Molecular Biology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/b6828f826e2c9257aff3c44068f85720e5f1356f

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Citations in the corpus

Religious Orders Study and Rush Memory and Aging Project (2018, positive): “The string of failed studies is long despite the investment of billions of dollars from the public and private sectors, the participation of many tens of thousands of people in clinical trials, and the efforts of thousands of researchers and study staff [440].”
Alzheimer’s disease: experimental models and reality (2017, background): “6%), many of which were successful in preclinical testing using these animal models [6, 27, 139].”
Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA (2015, background): “Furthermore, a recent meta-analysis has shown that relatively few clinical trials are being undertaken for AD therapeutics, and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area (Cummings et al., 2014), highlighting the importance of developin”
2016 Alzheimer's disease facts and figures (2016, neutral): “gov, a National Institutes of Health registry of publicly and privately funded clinical studies [106].”