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- Alzheimer’s Disease
Alzheimer’s Disease is a progressive degenerative brain disorder that destroys brain cells, causing memory loss and problems with thinking and behavior severe enough to affect work, lifestyles or social life. Alzheimer’s gets worse over time, and it is fatal.
Alzheimer’s Disease is the most common dementia among older adults. As many as 5.3 million people in the United States are living with Alzheimer’s, with that number expected to grow to 14 million by 2050.
A landmark report on the Global Economic Impact of Dementia finds that Alzheimer’s Disease and other dementias are exacting a massive toll on the global economy, with the problem set to accelerate in coming years.
No treatment is available to slow or stop the deterioration of brain cells in Alzheimer’s Disease. The U.S. Food and Drug Administration has approved five drugs that temporarily slow the worsening effects of the symptoms for 6 to 12 months, on average, for about half of the individuals who take them. There remains a significant medical need in Alzheimer’s Disease.
For an overview of Alzheimer’s Disease, please click here.
Anavex is developing novel treatments that are currently undergoing late pre-clinical investigation.
Mode of action: In AD, ANAVEX 2-73 has shown a best-in class profile, due to its potency in validated animal models, no toxicity to date in exhaustive animal testing, novel mode of action and its potential to blunt endoplasmic reticulum (ER) stress, mitochondrial stress and oxidative stress, thought to be contributory causes of AD. Research in recent years indicates that oxidative stress is a precursor to amyloid-beta plaques and tau (Neuro-Fibrillary Tangles or NFT), and that protecting against oxidative stress may help to prevent or slow the disease.
Results to date: Successfully completed a Phase 1 single ascending dose (SAD) clinical trial. In this phase, the maximum tolerated single dose was defined per protocol as 55-60 mg. This dose is above the equivalent dose shown to have positive effects in mouse models of AD. There were no significant changes in laboratory or electrocardiogram (ECG) parameters. ANAVEX 2-73 was well tolerated below the 55-60 mg dose with only mild adverse events in some volunteers. Observed adverse events at doses above the maximum tolerated single dose included headache and dizziness, which were moderate in severity and reversible. These side effects are often seen with drugs that target central nervous system (CNS) conditions, including AD.
About the ANAVEX 2-73 Phase 1 Clinical Trial: The ANAVEX 2-73 Phase 1 trial was conducted as a randomized, placebo-controlled study. Healthy male volunteers between the ages of 18 and 55 received single, ascending oral doses over the course of the trial. Study endpoints included safety and tolerability together with pharmacokinetic parameters. Pharmacokinetics includes the absorption and distribution of a drug, the rate at which a drug enters the blood and the duration of its effect, as well as chemical changes of the substance in the body. This study was conducted in Germany in collaboration with ABX-CRO, a clinical research organization that has conducted several Alzheimer’s Disease studies, and the Technical University of Dresden.
Moving forward: We hope to begin a Phase 2a clinical trial in Alzheimer’s Disease patients later this year, which would deliver safety and efficacy data in human subjects, including patients, provided the timelines are achieved with no unforeseen delays.
ANAVEX 19-144 is the active metabolite of ANAVEX 2-73, which not only adds further beneficial effects as above, but also confers a longer duration of action.
Mode of action: ANAVEX 1-41 presents a mixed pharmacological activity involving the modulation of sigma-1 and muscarinic components showing prominent anti-amnesic, anti-depressant and weak anti-convulsive activity at low sigma-1 agonistic doses. In addition, it presents mixed pharmacological activity involving the modulation of sigma-1 receptors as well as sodium and chloride channels showing neuroprotection.
Results to date: preclinical tests revealed significant neuroprotective benefits through the prevention of oxidative stress, which damages and destroys cells and is believed to be a primary cause of Alzheimer’s Disease. In addition, ANAVEX 1-41 prevented the expression of caspase-3, an enzyme that plays a key role in apoptosis (programmed cell death) and in the loss of cells in the hippocampus, the part of the brain that regulates learning, emotion and memory. These activities involve both sigma-1 and muscarinic receptor systems through a novel mechanism of action.
Moving forward: The company has initiated scale-up manufacturing of ANAVEX 1-41, its second lead compound. With sufficient quantities of ANAVEX 1-41 in hand we will be in a position to advance the program and begin preclinical studies on large animals in the near term. This is expected to take ANAVEX 1-41 an important step closer to Phase 1 trials in humans.
The required quantities of ANAVEX 1-41 will be manufactured by Syntagon AB under GMP conditions, the quality assurance system required in the production of medicinal products.
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