Alzheimer's drug-development pipeline: 2016.

BACKGROUND: Alzheimer's disease (AD) is growing in frequency and new therapies are urgently needed. METHODS: We assessed clinicaltrials.gov (accessed 1-4-2016) to determine the number and characteristics of trials in phase I, phase II, and phase III for treatment of AD. RESULTS: There are currently 24 agents in 36 trials in phase III of AD drug development. Seven of these 24 agents are symptomatic cognitive-enhancing compounds, and 17 are disease-modifying treatments (DMTs). Most DMTs address amyloid-related targets (76%). There are 45 agents in phase II being assessed in 52 clinical trials. Phase II trials include 30 DMTs, with 26 small molecules and 4 immunotherapies. There are 24 agents in the first phase of AD drug development. DISCUSSION: Amyloid is the principal target of late-stage development programs. There are relatively few agents in clinical trials for AD suggesting a need to amplify the drug discovery ecosystem.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.