Medical Food for Alzheimer's Disease Launched in United States, But Alzheimer's Association Urges Caution

Susan Jeffrey

March 12, 2009

March 12, 2009 — A new product deemed a medical food by the Food and Drug Administration is now available in the United States, the manufacturer, Accera, has announced.

Known by the brand name Axona, the food targets metabolic deficiencies associated with Alzheimer's disease (AD). It has been shown in a phase 2 clinical trial to improve cognition and memory in patients with mild to moderate disease, a statement from the company notes. Dispensed by prescription, it comes in single-serving packets and is taken once daily mixed with water.

"By approaching the disease in a new way, Axona addresses a metabolic abnormality of Alzheimer's disease that has not previously been examined," Jeffrey L. Cummings, MD, director of the Mary S. Eaton Center for Alzheimer's Disease Research at the University of California, Los Angeles and a consultant to Accera, said in the company statement. "The goal of therapy is to optimize cognitive function."

However, the Alzheimer's Association has taken a cautious stance with regard to the new product, pointing out that phase 2 results often have not persisted in phase 3 testing, leaving questions about what it will actually offer to patients.

"It's very unlikely the product will be covered under any kind of insurance reimbursement, so that suggests that people will be using their own money for it, and I think it's not quite clear whether they will be getting any kind of value or benefit," William H. Thies, PhD, vice president for medical and scientific relations at the Alzheimer's Association, told Medscape Neurology & Neurosurgery.

Medical Foods

A medical food is an FDA-regulated product, the Accera release states, in a relatively new category of medical protocols defined by Congress as part of the Orphan Drug Act. Medical foods were defined in 1988 as a special category of products intended for the specific dietary management of a disease or condition that has distinctive nutritional requirements, established by medical evaluation. Prior to 1988, the company notes, medical foods were regulated as drugs.

Premarket scientific testing is required to demonstrate the product meets the specific nutritional needs in a particular condition, testing that includes clinical trials, the company notes.

At the 2007 Alzheimer's Association International Conference on Prevention of Dementia (ICAD), the company presented findings from a phase 2 double-blind, randomized, multicenter, placebo-controlled trial in 152 patients with probable mild to moderate AD. The trial was funded by Accera.

In AD, there is a substantial decrease in the brain's ability to metabolize glucose, which contributes to the clinical and pathological course of disease, the company statement notes. The product is metabolized and forms the ketone body β-hydroxybutyrate (BHB), providing neurons with an alternative to glucose, the researchers wrote in their ICAD abstract.

Results of the trial showed those taking Axona (then called Ketasyn) had significant improvement in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) at day 45 (P = .024), which was maintained through day 90, although the difference was no longer significant at that point (P = .0767).

The difference in ADAS-cog was significant at both day 45 (P < .0005) and at day 90 (P = .015) in a subset of APOE e4–negative patients.

The most common adverse events were diarrhea, flatulence, and dyspepsia, according to safety information for healthcare providers on the company's Web site. No significant interactions were seen with commonly prescribed AD drugs, including donepezil (Aricept, Esai Co) and/or N-methyl-D-aspartic acid (NMDA)–receptor agonists such as memantine (Namenda, Forest Laboratories).

The product contains caseinate, whey, and lecithin, and thus contains milk and soy, the company adds. It should be used with caution in patients with known hypersensitivity to palm or coconut oil, those at risk for ketoacidosis, or those with a history of gastrointestinal inflammation, metabolic syndrome, and/or a history of renal dysfunction.

A Growing Area

Dr. Thies pointed out that other similar products are in development, and the Alzheimer's Association expects this to be "a growing area." At the 2008 ICAD meeting, for example, findings with another product in development called Souvenaid (Danone Research) were presented. The product, a once-a-day drink, combines substances including uridine monophosphate, choline, and omega-3 fatty acids, vitamins, and antioxidants with a view to improving cognitive function.

Results in mild Alzheimer's patients showed statistically significant benefit on a delayed verbal memory task derived from the Wechsler Memory Scale–revised. No significant effect was seen on the ADAS-cog in unadjusted analyses, although there did appear to be an effect in the subgroup of patients with higher baseline ADAS-cog scores.

"I think for all of those, there should be tremendous caution," Dr. Thies said. "One of the things that is clear about the characteristics of a medical food is that it is expected to be used under the regular care of a physician, so whoever is interested in using this type of material should discuss it carefully with their own physician and make sure that the physician and the patient and family understand what the rules are for use and the consequences.

"My guess is that given the amount of desperation that Alzheimer's breeds there will be some part of the population that will try this particular therapy, and I think it's trying it with way less data than we have for ethical pharmaceuticals," he added. "It's going to be harder to tell what the conclusions are, because people are trying it in a more or less random way, and it's very hard to quantitate that over a period of time."

A spokesperson for the company countered that it is the position of the company that the product has been shown to be safe and effective in a double-blind placebo-controlled clinical trial and achieved "self-affirmed [Generally Regarded as Safe] GRAS FDA status.

"Early in Accera's launch, [the company] is encouraged by the response in the physician community to the potential benefits of Axona," she told Medscape Neurology & Neurosurgery in an emailed comment. "Accera is a strong supporter of the Alzheimer's Association and is working with them to address their concerns."

The company is "always interested in further scientific investigation of Axona and may consider future investigative studies," she added.

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