While most of the industry focuses on beta amyloid and tau as targets for Alzheimer's disease, Accera Inc. has turned its attention to a deficit in the ability of Alzheimer's patients' brain cells to metabolize glucose.

While most of the industry focuses on beta amyloid and tau as targets for Alzheimer's disease, Accera Inc. has turned its attention to a deficit in the ability of Alzheimer's patients' brain cells to metabolize glucose.

Is hypometabolism a cause or just a symptom of Alzheimer's disease? There's some evidence that a reduction in the ability of brain cells to metabolize glucose could be an early event in the disease progression, but "the jury is still out," Samuel Henderson, VP of Research & Development at Accera told BioWorld Insight.

Whether it's a primary or secondary issue, Henderson pointed out the defect is "very amenable to intervention." In addition to processing glucose, brain cells can also be nourished with ketone bodies. In fact, fasting produces ketones primarily to feed the brain because it doesn't metabolize fat sources like other cells.

Accera already has a product, Axona, available as a medical food that induces therapeutic levels of ketosis. Axona is distributed through the pharmacy channel and like drugs requires a prescription.

Medicare currently doesn't cover medical foods, although there's a push in Congress to change that, but medical foods are covered by some private insurers. Other examples include phenylalanine-free diets for patients with phenylketonuria and Abbott's Pedialyte for dehydration in children.

In a double-blinded, placebo-controlled, clinical trial, Axona improved Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) scores after 90 days while the cognitive function of patients receiving placebo decreased. The difference was more substantial in patients with APOE4 mutations, a risk factor for Alzheimer's disease that affects lipid transport.

Even with the clinical trial data, Accera still has an uphill battle with Axona being classified as a medical food, a relatively unknown class of treatment. "There's a fair amount of education that has to go along with that," Henderson said.

Accera is developing a more tolerable formulation of caprylic triglyceride, dubbed AC-1204, under the standard investigational new drug pathway. That would allow AC-1204 to be marketed as a drug although Accera hasn't yet made a decision whether to follow that route or sell it as a medical food.

A randomized, placebo-controlled, double-blind clinical trial testing AC-1204 in patients with mild to moderate Alzheimer's disease is set to enroll its first patients in the first quarter of 2013.

Even though Axona was proven effective after just 90 days, Accera elected to do a longer 26 week study with an optional 26 week open-label extension. "We got lots of feedback from KOLs that they wanted to see longer-term data," Henderson said.

Even 26 weeks is shorter than other Alzheimer's disease clinical trials run recently. Pfizer Inc. and Johnson & Johnson's trials testing bapineuzumab measured efficacy after 18 months. Ditto for Eli Lilly and Co.'s solanezumab. (See BioWorld Today Aug. 8, 2012, and Aug. 27, 2012.)

But Henderson said the longer trials were mainly required because of poor treatment effects observed in Phase II trials. "Other drugs need longer trials to see a drop in the placebo group," Henderson said. "I'm very confident to we'll see a treatment effect after 26 weeks."