Following a positive review of preliminary data, an independent board recommended the Phase 2b/3 study investigating oral Anavex 2-73 (blarcamesine) in people with early Alzheimer’s disease continue without modification.
As specified in trial protocol, the Independent Data Safety Monitoring Board (DSMB) — used in ongoing clinical trials to protect patients and the integrity of study data — reviewed interim safety data for the Anavex 2-73-AD-004 trial (NCT03790709) and its open-label extension, called ATTENTION-AD (NCT04314934), before favoring their continuation.
Alzheimer’s, a progressive neurodegenerative disorder characterized by nerve cell death for reasons not yet clear, is thought to be due to amyloid plaques and tau tangles — which are clumps of misfolded protein that disrupt normal cell function.
Anavex 2-73, being developed by Anavex Life Sciences, is a small molecule designed to activate a receptor called sigma-1. Alzheimer’s patients have fewer of these receptors in their brains compared to people of the same age without the disorder.
Activation of sigma-1 may lessen clinical symptoms, marked by a progressive loss of the ability to learn, communicate, reason, and carry out daily activities. Activation is also thought to protect against neurologic changes by targeting protein misfolding, problems with mitochondria (a cell’s energy producers), inflammation, and oxidative stress — an imbalance between the production of metabolic byproducts, such as reactive oxygen species, and a cell’s ability to detoxify them.
Preclinical animal studies demonstrated Anavex 2-73’s potential to stop or reverse Alzheimer’s progression. Its use also showed protection against convulsions, amnesia, neurological damage, and depression, suggesting it might also treat other conditions, including Parkinson’s disease and epilepsy.
Positron emission tomography (PET) brains scans have confirmed a dose-dependent interaction between Anavex 2-73 and sigma-1 receptors.
Anavex 2-73-AD-004 is a placebo-controlled safety and efficacy study underway in Australia, Canada, Germany, the Netherlands, and the U.K., with more than 92% of its estimated 450 patients enrolled. Participants are those with cognitive impairment, or early stage and mild dementia, due to Alzheimer’s, ranging in age from 60 to 85. More information about site locations and contacts is here.
Patients are being randomly assigned to one of two oral doses (a moderate and high dose) of Anavex 2-73, or to a placebo for about one year (48 weeks).
The trial’s primary goals are changes from the study’s start in cognitive ability as measured by the Alzheimer’s Disease Assessment Scale in cognition (ADAS-Cog), and in patients’ ability to go about daily life activities, measured using the Alzheimer’s disease cooperative study-activities of daily living (ADCS-ADL). Safety and tolerability are being monitored as well.
Questionnaires are regularly assessing sleep continuity and life quality for both patients and caregivers. Cerebrospinal fluid and blood samples are also being collected to monitor biomarkers before and after treatment, some of which were identified in the previous Anavex 2-73-002 Phase 2a study (NCT02244541).
This study demonstrated dose-dependent improvement in endpoints of cognition and function.
Patients who complete Anavex 2-73-AD-004 will be invited to enroll in the open-label ATTENTION-AD study, in which all will be given the treatment for two years.