Eli Lilly, AstraZeneca end late-stage studies of BACE inhibitor lanabecestat

Eli Lilly and AstraZeneca announced Tuesday that they will halt Phase III studies of lanabecestat for the treatment of Alzheimer's disease after an independent Data Monitoring Committee (DMC) determined that trials of the BACE inhibitor were not likely to meet their primary endpoints upon completion and should be stopped for futility. The companies noted that the DMC's recommendation to end the studies early was not based on safety concerns.

According to Eli Lilly and AstraZeneca, both the AMARANTH trial, in early Alzheimer's disease, and the DAYBREAK-ALZ study, in mild Alzheimer's disease dementia, will be halted. In addition, the related AMARANTH extension trial will also be discontinued. Daniel Skovronsky, president of Lilly Research Labs, said the companies are "deeply disappointed" on the outcome, adding "the complexity of Alzheimer's disease poses one of the most difficult medical challenges of our time."

The AMARANTH trial randomised patients with early Alzheimer's disease to receive one of two doses of lanabecestat or placebo orally once daily for 104 weeks, while the DAYBREAK-ALZ study randomised patients with mild Alzheimer's disease dementia to receive the BACE inhibitor at one of two doses or placebo orally once daily for up to 156 weeks. The main goal of both trials was change from baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13).

In 2014, Eli Lilly and AstraZeneca entered an alliance for the development and commercialisation of lanabecestat, with the former leading clinical development. Under the deal for the drug, formerly called AZD3293, AstraZeneca would be responsible for manufacturing.

Commenting on the latest news, Shore Capital analyst Tara Raveendran said "although clearly disappointing for the field, there were fairly low expectations for the trial," adding "this reflects the difficulties that have been encountered in drug development for Alzheimer's disease with a number of disappointments to date." Last month, Johnson & Johnson scrapped development of atabecestat after serious elevations of liver enzymes were seen in some patients given the BACE inhibitor, while earlier this year, Merck & Co. ended a Phase III study of verubecestat, after an external DMC concluded that the BACE1 inhibitor was unlikely to exhibit a positive benefit/risk ratio if the trial continued.

However, more recently, Biogen and Eisai reported that in a mid-stage study, the experimental oral drug elenbecestat demonstrated a significant difference compared to placebo in amyloid beta levels in the brain in patients with mild cognitive impairment due to Alzheimer's disease, or mild-to-moderate dementia due to Alzheimer's disease. The companies suggested that the trial is the first of a BACE inhibitor "to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory endpoints." Two Phase III studies of elenbecestat in early Alzheimer's disease are currently under way.

For related analysis, see ViewPoints: Eisai, Biogen offer sign of life for BACE inhibition.

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