Date: 2016-04-08
Type of information: DSMB assessment
phase: 2-3
Announcement: DSMB assessment
Company: AstraZeneca (UK) Eli Lilly (USA - IN)
Product: AZD3293/LY3314814
Action
mechanism: BACE (beta-site APP-cleaving enzyme-1) inhibitor. AZD3293 is an oral beta secretase cleaving enzyme (BACE) inhibitor. BACE is an enzyme associated with the development of amyloid beta. Inhibiting BACE is expected to prevent the formation of amyloid plaque and eventually slow the progression of the disease. AZD3293 is an oral, potent and selective small molecule inhibitor of BACE that has been shown in Phase I studies to significantly and dose-dependently reduce levels of amyloid beta in the cerebro-spinal fluid of Alzheimer’s patients and healthy volunteers. AstraZeneca and Lilly announced an alliance in 2014 for the development and commercialization of AZD3293. Under the agreement, Lilly will lead clinical development, working with researchers from AstraZeneca's Research and Development Team, while AstraZeneca will be responsible for manufacturing. The companies will take joint responsibility for commercialization of the molecule and will share all future costs equally for development and commercialization, as well as net global revenues post-launch.
Disease: Alzheimer´s disease
Therapeutic area: Neurodegenerative diseases
Country: Argentina, Australia, Belgium, Canada, Czech Republic, France, Hungary, Japan, Germany, Poland, S Korea, Romania,Spain, UK, USA
Trial
details: AMARANTH is a Phase II/III study that will further investigate the safety of AZD3293/LY3314814 and subsequently test the hypothesis that it is a disease-modifying treatment for patients with early Alzheimer´s disease. Early Alzheimer’s disease is defined as the continuum of patients with mild cognitive impairment (MCI) due to Alzheimer´s disease and patients diagnosed with mild Alzheimer´s dementia. The study, which has a two-year treatment period, aims to enrol more than 1500 patients in 15 countries. (NCT02245737)
Latest
news: * On April 8, 2016, AstraZeneca and Eli Lilly announced that AMARANTH, a Phase II/III study of AZD3293, an oral beta secretase cleaving enzyme (BACE) inhibitor currently in development as a potential treatment for early Alzheimer’s disease, will continue into Phase III of the Phase II/III seamless trial. The AMARANTH independent data monitoring committee recommended the study continue without modification after a scheduled interim safety analysis was conducted. The analysis was not designed to review efficacy. AstraZeneca and Lilly have also announced the planned initiation of a new Phase III trial for AZD3293. The trial, named DAYBREAK, will study the safety and efficacy of AZD3293 in people with mild Alzheimer’s dementia. DAYBREAK will begin enrolling participants in the third quarter of 2016. Under the terms of the agreement, AstraZeneca will receive a further milestone payment from Lilly now that AZD3293 will move into Phase III testing. The payment of $100 million will be reported as Externalisation Revenue in AstraZeneca’s financial statements and does not change the financial guidance for 2016. * On December 1, 2014, AstraZeneca and Eli Lilly announced enrolment of the first patient into AMARANTH, a Phase II/III study of an oral beta secretase cleaving enzyme (BACE) inhibitor currently in development as a potential treatment for Alzheimer’s disease. AZD3293, also known as LY3314814, has been shown in Phase I studies to reduce levels of amyloid-beta in the cerebro-spinal fluid of Alzheimer’s patients and healthy volunteers. 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. The pivotal study will investigate the safety and efficacy of AZD3293/LY3314814 compared with placebo in the treatment of early Alzheimer’s disease. AstraZeneca and Lilly announced an alliance earlier in 2014 for the development and commercialisation of AZD3293/LY3314814. Under the agreement, Lilly will lead clinical development, working with researchers from AstraZeneca’s Neuroscience Innovative Medicines Unit, while AstraZeneca will be responsible for manufacturing. The companies will take joint responsibility for commercialisation of the molecule and will share all future costs equally for development and commercialisation, as well as net global revenues post-launch.
