Ketasyn Improves Memory In Age-Associated Memory Impairment Study
Recent data from a Phase II study of Accera's lead compound Ketasyn (AC- 1202) in age-associated memory impairment showed that Ketasyn has a positive and clinically meaningful effect on memory in older adults.
AAMI is the decline in memory that occurs during the natural course of aging, The National Institute of Mental Health criteria for AAMI include complaints of gradual memory loss in everyday problems in persons more than 50 years of age. AAMI affects an estimated 10-15 million people in the U.S., and may be a precursor to Alzheimer's disease (AD), which is expected to afflict 11-16 million Americans in the next 40 years.
AAMI symptoms may be related to declines in glucose metabolism in the brain that are also associated with aging. Glucose is the brain's primary fuel source, so aging brains with impaired glucose metabolism require an alternative source of energy. Ketasyn is an orally available compound that is metabolized into ketone bodies, which the brain can use for energy even when its ability to process glucose is impaired.
"The results of this study support the hypothesis that providing additional energy reserves to the elderly brain improves a variety of cognitive activities. They also provide further evidence of the roles that glucose and insulin metabolism plays in cognition and memory," said Dr. Lauren Costantini, Accera's vice president of clinical development. "As in our earlier successful clinical studies in Alzheimer's disease, Ketasyn was well tolerated by subjects in the AAMI study and we are encouraged by the strong efficacy data."
The randomized, double-blind, placebo-controlled, parallel, multi-center trial was conducted at six centers in the United States. One hundred fifty- nine subjects diagnosed with AAMI received either Ketasyn or placebo for 90 days followed by a two-week washout period. Mean age in this study was 65. Subjects underwent genomic testing for variations in the coding regions of genes known to influence memory and cognition, including the apolipoprotein E gene (APOE), a known genetic risk factor for Alzheimer's disease (AD) that occurs in 15-20% of the general population. On days 0, 30, 60, 90 and 104, subjects were evaluated through a battery of neuropsychometric tests that measure various aspects of memory and cognition.
Ketasyn showed significant efficacy in tests of memory. On average, subjects taking Ketasyn performed significantly better on the 'First-Last Name Association' test (FLN) than subjects taking placebo (p=0.042). "On average, seniors taking Ketasyn remembered more names than those taking placebo," said Dr. Costantini.
In another memory test called Name-Face Recognition (NFA), which associates a person's name and face, Ketasyn subjects under age 59 improved significantly more than placebo subjects at Day 90 (p=0.0217). The efficacy in the NFA test observed with Ketasyn in subjects under age 59 captures a large portion of the AAMI population.
Consistent with the findings of Accera's Phase IIa and IIb AD studies, subjects who did not have the APOE4 genotype (E4(-)) responded particularly well to treatment: E4(-) subjects showed a further significant treatment effect of Ketasyn in FLN at Day 90 (p=0.012). In contrast, and also consistent with the AD trial results, APOE4(+) subjects showed no difference between Ketasyn and placebo for FLN scores at Day 90 (p=0.4639).
The safety profile of Ketasyn was excellent, as shown in the previous AD trials with Ketasyn. The incidence of adverse events was low and similar between Ketasyn and placebo groups.
Accera recently completed a Phase IIb clinical trial in AD patients that confirmed Ketasyn's safety and efficacy as measured by improvement in ADAS-Cog scores, the gold standard measure for efficacy in cognition and short-term memory. Accera plans to initiate a pivotal, Phase III multi-center clinical trial in early 2008 in mild-to-moderate AD patients. This study will focus on several measures of efficacy, including ADAS-Cog, safety and the role of insulin regulation in AD.
Brain imaging techniques performed on aging adults and Alzheimer's patients reveal a dramatically decreased uptake of glucose, the brain's preferred source of energy. Ketasyn (AC-1202) is an orally available compound that is efficiently metabolized by the liver into ketone bodies, an alternative energy source that the brain can utilize when glucose metabolism is compromised. Ketasyn has disease modifying potential in AD and a number other neurodegenerative diseases characterized by decreased glucose use in the brain, which is known as neuronal hypometabolism.