Lilly Kills a BACE Inhibitor Trial for Alzheimer’s

Eli Lilly recently announced that they voluntarily halted a Phase II clinical trial for LY2886721, a beta secretase (BACE) inhibitor designed to slow down the progression of Alzheimer’s disease.

The Lilly announcement indicated that the trial was halted due to abnormal liver test results in patients. It’s not clear if BACE inhibition itself was causing the toxic liver test results, or if it was something in the way the drug molecule was designed.

As discussed in our report on early detection tests for Alzheimer’s disease, BACE inhibitors do show some promise in slowing or halting Alzheimer’s progression, but the safety of these drugs is a big unknown. In addition to controlling the formation of amyloid beta protein in the brain, BACE is also involved in the development of myelin sheathes — the “insulation” surrounding axons.

Demyelination (the loss of protective myelin sheathes) can result in serious disorders like multiple sclerosis (MS) and Guillain-Barr√© syndrome. The other drug companies pursuing BACE inhibitor trials (Merck, Roche, Pfizer, AstraZeneca) will need to tread very carefully to make sure that shutting down amyloid beta formation doesn’t also block the brain’s ability to create and maintain protective myelin.