AstraZeneca and Eli Lilly end disappointing Alzheimer's trials

AstraZeneca, alongside its partner Eli Lilly and Company, announced on Tuesday the discontinuation of the global Phase III clinical trials of lanabecestat, an oral beta secretase cleaving enzyme (BACE) inhibitor, for the treatment of Alzheimer's disease.

The FTSE 100 drugmaker said the decision was based on recommendations by an independent data monitoring committee, which concluded that both the AMARANTH trial in early Alzheimer's disease and the DAYBREAK-ALZ trial in mild Alzheimer's disease dementia were not likely to meet their primary endpoints upon completion, and therefore should be stopped for futility.

As a result of the decision, the related AMARANTH extension trial would also be discontinued.

“We are saddened by this outcome as our researchers are working tirelessly to find a solution for the many people who are impacted by this devastating disease,” said Menelas Pangalos, executive vice-president of AstraZeneca’s IMED biotech unit.

“We are committed to ensuring our findings can be used to inform further research in the Alzheimer's community, given the importance of finding a treatment for this disease.”

The independent data monitoring committee recommendation to stop the studies was not based on safety concerns, AstraZeneca said.

It added that the AstraZeneca and Lilly BACE alliance for lanabecestat remained in place, and the companies would now work with the clinical trial sites involved to implement the discontinuations.

“The complexity of Alzheimer's disease poses one of the most difficult medical challenges of our time, and we are deeply disappointed for the millions suffering from this devastating disease," said Daniel Skovronsky, president of Lilly Research Labs.

“We are grateful for the contributions of the study participants and their families and encourage them to consider other Alzheimer's disease clinical trials.”

Skovronsky said Eli Lilly remained dedicated to Alzheimer's disease research, as it had been for the last three decades.

“We won't give up on finding a solution for Alzheimer's patients.”

The AMARANTH trial randomised patients with early Alzheimer's disease to receive lanabecestat - 20mg or 50mg - or placebo orally once daily for 104 weeks.

According to the two firms, the primary endpoint of the trial was change from baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13).

Early Alzheimer's disease was defined as the continuum of patients with mild cognitive impairment due to Alzheimer's disease and patients diagnosed with mild Alzheimer's disease dementia.

Patients who completed the AMARANTH trial were given the opportunity to enrol in the AMARANTH extension trial, where all patients received active treatment.

The DAYBREAK-ALZ trial randomised patients with mild Alzheimer's disease dementia to receive either lanabecestat - 20mg or 50mg - or placebo orally once daily for 156 weeks.

For that trial, the primary endpoint of the trial was change from baseline on ADAS-Cog13.

AstraZeneca said the discontinuation of the lanabecestat Phase III clinical trials in Alzheimer's disease was not expected to have a material impact on its financial guidance for 2018, which therefore remained unchanged.