The Alzheimer's Clinical Trials Consortium (ACTC), a clinical trial network focusing on studies for therapies in Alzheimer’s disease (AD), selected two drug candidates to enter the clinic. The trials will be conducted with grant funding by the National Institute on Aging at the National Institutes of Health.
Elenbecestat an investigational oral beta amyloid cleaving enzyme (BACE) inhibitor will enter the clinic with the investigational anti-amyloid beta (Ab) protofibril antibody, BAN2401. Clinical studies for the two drugs will target the primary prevention (A3 Study) and secondary prevention (A45 Study) of AD and are set to begin in 2020. Each trial will require at least 400-600 participants.
The consortium, based at the University of Southern California, Harvard University and the Mayo Clinic, selected the two drug candidates to enter the clinic following its mission to accelerate and expand studies for therapies in AD and related dementias.
ACTC's co-principal investigator, Paul Aisen told us the drugs have 'enormous potential', particularly when administered very early in the disease course. The A3 and A45 studies will both involve individuals who are clinically and cognitively normal, but with sub-threshold (not elevated, but at high risk for becoming elevated, in the A3 trial) or elevated brain amyloid (in A45).
"Elenbecestat is expected to prevent the accumulation of brain amyloid in sub-threshold individuals, while BAN2401 is expected to dramatically reduce brain amyloid in individuals with elevated levels. They each have the potential to slow the development of symptoms related to Alzheimer’s disease," Aisen said.
Speaking on the two-drug approach, Aisen explained that "BAN2401 can dramatically reduce (or normalize) brain amyloid load, but it must be administered by intravenous infusion. Elenbecestat is given by mouth, and effectively inhibits the generation of amyloid (but does not dramatically reduce brain amyloid load."
"The two drugs will be used sequentially in the A45 trial to normalize brain amyloid (with IV BAN2401) and then prevent reaccumulation (with oral elenbecestat). Elenbecestat alone will be used in the A3 trial to prevent amyloid accumulation in individuals with sub-threshold levels," he added.
The complexity of AD has led a number of high profile clinical trial failures. A Biogen executive had stated to us that the difficulties in development were due to a lack of knowledge.
Earlier this year, Biogen stopped its ongoing development of aducanumab, a potential AD treatment under clinical trial investigation run in partnership with Eisai, due to an independent monitoring committee’s suggestion that the trial was unlikely to succeed.
Advanced Clinical a contract research organization will partner with Cognitive Clinical Trials to expedite additional studies related to AD and overcome obstacles in this research field.
