Partners Eisai and Biogen ($BIIB) are moving their oral beta-secretase cleaving enzyme (BACE) inhibitor E2609 into Phase III. There they join other major biopharmas looking to use BACE inhibitors to prevent the buildup of beta-amyloid in an effort to slow or halt the progression of Alzheimer’s disease.
Among the most advanced are Merck ($MRK), which is in Phase II/III testing for its BACE inhibitor MK-8931 in a placebo-controlled Phase II/III trial in almost 2,000 mild to moderate Alzheimer’s disease patients, while partners AztraZeneca ($AZN) and Eli Lilly ($LLY) have moved into the Phase III portion of a Phase II/III trial for oral BACE inhibitor AZD3293 in early Alzheimer’s disease.
The Eisai/Biogen candidate, E2609, was already in a Phase II randomized, placebo-controlled trial known as Study 202. Eisai and Biogen presented the study results to the FDA. The agency confirmed that the data were “sufficient to commence Phase III studies,” the partners said.
“The Phase III clinical study design outline agreed upon will enable us to efficiently conduct studies on BACE inhibitors aimed at realizing preemptive medicine, and will accelerate the development of E2609,” said Eisai Neurology Business Group CCO and CMO Dr. Lynn Kramer in a statement. “We are striving to deliver E2609 to patients around the world as soon as possible, and contribute to increasing the benefit for patients.”
The Phase III study will be in early Alzheimer’s disease patients with an E2609 dosage of 50 mg/day for the treatment group. This is the highest of the three doses tested in the dose-ranging Phase II trial. The primary endpoint will be based on the dementia assessment tool the Clinical Dementia Rating Sum of Boxes (CDR-SB).
Study 202 tested plasma and cerebrospinal fluid (CSF) for amyloid beta; it also confirmed accumulation of amyloid beta by PET (positron emission tomography) screening. The trial found that E2609 was safe at all tested doses and that amyloid beta levels in plasma and CSF reduced in a dose-dependent fashion.
Eisai and Biogen originally partnered on E2609 in a 2014 collaboration that was updated last year. The partners split R&D costs equally, with profits to be evenly split as well.
BACE inhibition remains controversial as a strategy to treat the ever-elusive and seemingly intractable Alzheimer’s disease. It’s still unclear if inhibiting the accumulation of amyloid beta will effectively deter its symptoms. In addition, BACE also has other functions in the body, including helping to ensure muscle function. So, even if this class can prove effective as an Alzheimer’s treatment, the unintended effects could prove a safety problem.