During a forum discussion session at the Alzheimer's & Parkinson's Disease (AD/PD) Congress 2017, the panel of corporate executives from the leading players in Alzheimer's disease (AD) research, including Eli Lilly, Roche, Janssen, Eisai, and Biogen, discussed the lessons learned from the past failures and strategies for achieving success in the late stages of AD drug development. In response to some difficult questions from the audience, the panel highlighted targeting the wrong patient population, lack of biomarkers, and insufficient understanding of drugs’ mechanisms of action as some of the key contributors to the recent failures. They emphasized that companies must have clear strategies from early trial phases to tackle these challenges and to succeed in AD drug development.

The key success factors and strategies discussed by the panel included the following:

  • Have a large patient enrollment in the trial: The new trend in Phase III AD trials is to recruit a large number of early-stage AD patients to maximize the statistical power and to detect treatment effect. Recruitment of many participants requires close patient engagement and active promotion using various media, such as social networking sites and on television.
  • Recruit early-stage AD patients: Following the recent failures of trials in mild to moderate AD patients, the focus has shifted to targeting patients at an earlier stage of disease progression, such as those presenting with mild cognitive impairment (MCI) and pre-symptomatic people with increased genetic susceptibility for AD. Enrolling non-patient population into trials will require the use of genetic biomarkers and cognitive tests that can accurately identify people who are likely to develop AD in the future. Use of registries from sources such as Brain Health Registry (HealthyBrains.org) and the Dominantly Inherited Alzheimer Network Trial (DIAN-TU) will further facilitate early patient enrollment.
  • Test exploratory biomarkers: Only three biomarkers—b-Amyloid, total tau, and phosphorylated tau in cerebrospinal fluid (CSF)—have been validated to date. Future trials will have to test a multitude of exploratory biomarkers to improve patient enrollment and to monitor and detect pharmacological effect over time. Promising biomarkers to be added to future Phase III trials include neurofilament light and tau-PET imaging.  
  • Share the data: An increasing number of initiatives, such as Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Centre (NACC), are collecting and sharing data freely for research use. Open communication and data sharing will be increasingly expected from research teams in the pharmaceutical sector, and without this, costly failures in late-phase trials cannot be avoided.

Given the challenges faced by all manufacturers pursuing AD trials, there was a unanimous emphasis that development of disease-modifying drugs is not a race, and that collaboration between academic institutions and pharmaceutical companies is key to finding a disease-modifying drug in the future.