Charting a path toward combination therapy for Alzheimer’s disease

Abstract

It is acknowledged that progress in combined therapeutic approaches for Alzheimer’s disease (AD) will require an unprecedented level of collaboration. At a meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer’s Disease Coalition and the Critical Path Institute, investigators from industry, academia and regulatory agencies agreed on the need for combinatorial approaches to treating AD. The need for advancing multiple targets includes recognition for novel adaptive trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination. A combination trial now being planned may test drugs targeting different pathogenic pathways or multiple targets along a common pathway. Collaborations and consortia-based strategies are pivotal for success and a regulatory framework is recommended for success.

Keywords:

• Alzheimer’s disease
• combination therapy
• collaboration
• novel therapy
• co-development

Financial & competing interests disclosure

M Krams is an employee of Janssen R&D. R Sperling is a consultant to Roche, Isis, Genentech, Janssen and has received research support from Eli Lily, Eisai, Avid and Janssen. J Luthman is an employee of Eisai Inc and owns shares in AstraZeneca & Merck Inc. F Owen Fields is employed by Pfizer and has stock options in Pfizer. S Salloway has received research support from Biogen Idec, Merck Lilly, Roche & Genentech. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• There is an urgent need for new therapies to treat Alzheimer’s disease (AD).

• AD drug development has focused primarily on a single therapeutic molecular mechanism over the past 25 years.

• Multiple molecular, biochemical and cellular pathways contribute to the pathophysiology of AD, suggesting that a combination of multiple targets is needed.

• Co-development of more than one drug candidate is encouraged by the US FDA and a regulatory framework was embraced.

• Examples and lessons learned in combination drug development for other complex diseases serve to pave the way for AD.

• Required tools and infrastructure for success necessitate collaboration, precompetitive data sharing and public–private partnerships.