Phase 3 Clinical Trial to Study Antibody for Alzheimer’s Disease

July 22, 2020 - Biogen and The Alzheimer’s Clinical Trials Consortium recently announced the start of a Phase 3 clinical study of  BAN2401, an antibody for individuals with preclinical Alzheimer’s disease (AD).  

Preclinical AD means that individuals have intermediate or elevated levels of amyloid in their brains. 

BAN2401 is a humanized, monoclonal, anti-Aβ, soluble aggregate antibody, which has the potential to have an effect on disease pathology and to slow the progression of AD. 

“It is hoped that initiating treatment much earlier in the disease process may be advantageous in preventing future cognitive decline” Reisa Sperling, MD, director at theCenter for Alzheimer Research and Treatment at Brigham and Women’s Hospital and co-principal investigator at theACTC, said in the announcement.

“The AHEAD 3-45 should provide critically important answers about the optimal time to intervene with anti-amyloid therapy.”

Currently, BAN2401 is being studied in AHEAD 3-45, a Phase 3 clinical study conducted as a public-private partnership between the ACTC and funded by the National Institute on Aging and Japanese pharmaceutical company Eisai.

The clinical trial will enroll nearly 1,400 participants and place them into one of two randomized, double blind, placebo-controlled trials, A45 and A3, based on the level of amyloid in the brain. 

The A45 trial will administer BAN2401 to unimpaired participants who have elevated levels of amyloid in the brain. The primary endpoint is the change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment.

In the A3 trial, unimpaired participants, have an intermediate amount of amyloid in the brain, and who are at high risk for further Aβ accumulation, will participate. The primary endpoint for A3 is change from baseline in brain amyloid levels as measured by amyloid PET.

Both trials include additional clinical assessment scales, imaging, blood biomarkers, and cerebrospinal fluid in a subset as exploratory endpoints, Biogen said.

An amyloid, tau, neurodegeneration biomarker panel of imaging and biofluid will be used to evaluate therapeutic effects on the progression of AD pathophysiologic changes.

“The initiation of AHEAD 3-45 with BAN2401, focused on therapies for the earliest stages of the AD continuum through our collaboration with the ACTC group, marks an exciting time for us,” says Lynn Kramer, MD, chief clinical officer of the Neurology Business Group at Eisai.

“This represents a next step in developing precision therapies for AD using biomarker panels as part of our human health care mission; we are committed to making a difference for patients, their families, and health care professionals across the globe.”

Many pharmaceutical companies have been joining the effort to uncover safe and effective treatments for AD, but some of the drugs and therapies developed have been ineffective thus far.

For example, at the beginning of June, a randomized clinical trial found that the antidepressant bupropion was not superior to a placebo for the treatment of apathy in patients with dementia of Alzheimer type without a depressed mood.

Specifically, results for the primary outcome measure showed no statistically significant effect of bupropion compared with placebo between baseline and 12 weeks.

Earlier this week, a JAMA Network Open study also reported that a daily dose of the dopamine agonist, rotigotine, showed no significant benefit from baseline to 24 weeks when compared with a placebo in patients with Alzheimer’s disease.

The estimated mean change in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score was 2.92 for the rotigotine group and 2.66 for the placebo group.

But for the secondary outcomes, there were significant estimated mean changes between groups for Alzheimer’s Disease Cooperative Study-Activities of Daily Living score, at −3.32 for rotigotine and −7.24 for the placebo group.