The trial will examine oral beta secretase cleaving enzyme (BACE) inhibitor AZD3293, also known as LY3314814, which reduced levels of amyloid-beta in the cerebro-spinal fluid of Alzheimer's patients and healthy volunteers in phase I studies.
Other potential Alzheimer's disease treatments have fallen by the wayside in recent years, including Lilly's gamma secretase inhibitor semagacestat, Bristol-Myers Squibb's avagacestat, as well as Pfizer and Johnson & Johnson's amyloid-targeting antibody bapineuzumab.
Merck is also working on its own BACE inhibitor, with its MK-8931 currently in phase II/III for mild-to-moderate forms of the disease.
The hope is that the BACE route could end the long run of failures experienced by the industry – which, in Lilly's case, has spanned 25 years of investigation into potential Alzheimer's candidates.
The progression of Alzheimer's disease is characterised by the accumulation of amyloid plaque in the brain. BACE is an enzyme associated with the development of beta-amyloid. Inhibiting BACE is expected to prevent the formation of amyloid plaque and eventually slow the progression of the disease.
Samantha Budd, vice president and head of Translational Science in AZ's Neuroscience Innovative Medicines Unit explained: "We believe that BACE inhibitors have the potential to target one of the key drivers of this devastating disease. Together with Lilly, we have unique expertise that will allow us to evaluate the potential of AZD3293 as a treatment for Alzheimer's patients."
The first patient enrolment in AMARANTH comes less than three months since the two pharma giants announced their alliance to development and commercialise AZD3293/LY331481 and aims to enrol more than 1,500 patients in 15 countries.
Lilly will lead clinical development, working with researchers from AZ's Neuroscience Innovative Medicines Unit, while AZ will be responsible for manufacturing. The companies will take joint responsibility for commercialisation and will share future costs and revenues equally.