When Gregory T. Martini stopped by his father's house one evening three years ago, he expected to do most of the talking. His father, a former engineer, had been diagnosed with Alzheimer's disease (AD) two years prior, a condition that had reduced his conversations to little more than “Hi, how are you?” So Martini was especially surprised when during this particular visit, his father initiated what turned into an 30-minute dialogue.
“I was amazed,” says Martini, 51, an attorney from Miami, FL. “It's one of those things that when you think back, you ask yourself, ‘Did it really happen?'”
What could have caused the 88-year-old to start acting like his old self again? According to Martini—and his father's doctor—the only factor that could account for the change was that his father had been prescribed a product called Axona two weeks earlier. Axona is a “medical food” manufactured by Accera and marketed for people with mild to moderate AD as improving cognitive function.
Martini, however, never had the chance to see any long-term improvement; three days after his visit, his father fell and broke his hip. It was an injury from which he never fully recovered before passing away last year.
While Martini remains a believer, the medical community has mixed feelings about whether Axona should be prescribed to people with AD. And with few effective treatments available for the symptoms of the disease, consumers may be particularly vulnerable to unsubstantiated marketing claims.
MEDICAL FOODS VS. PHARMACEUTICALS
Alzheimer's disease causes the brain to become less efficient at converting sugar (glucose) into energy. Some scientists believe this inefficiency may contribute to cognitive decline, although the research supporting this theory is preliminary. One animal study, for example, found that dogs fed an alternate form of glucose performed better on visual-spatial memory tasks and short-term memory tests. Axona counteracts the glucose-deprivation process, or so the theory goes, by providing caprylic triglyceride, an ingredient that the brain can use as an alternate energy source. The food comes in the form of a packet containing 20 g of powder that is mixed with 4–8 oz of water.
Introduced in 2009, Axona is currently the only medical food in the United States marketed for people with AD, although others are in development. Since the product is sold as a medical food and not a pharmaceutical drug, the manufacturer wasn't required to submit results from the same rigorous clinical trials that pharmaceutical companies must submit when seeking approval from the U.S. Food and Drug Administration (FDA) for a new drug. (Axona is not sold as a supplement either; even if it was, the FDA does not approve supplements.)
“The amount of evidence needed to sell a product as a medical food is considerably less than that needed to get approval for a pharmaceutical,” says William H. Thies, Ph.D., chief medical and scientific officer for the Alzheimer's Association. “If I wanted to create a medical food, I would formulate and test a theory about how the ingredients would work in the body. As long as the medical food is based on ingredients found in a regular diet, the FDA won't require evidence of effectiveness in advance of it going on the market.”
Accera published its research results in 2009 in the journal Nutrition & Metabolism. The study reported that of 152 people with mild to moderate AD, those who consumed the shake showed slightly better scores on cognitive tests than those who were given a placebo. The differences in scores were statistically significant.
However, the results of this study can be misleading for patients and neurologists alike, according to Gary Gronseth, M.D., professor and vice chairman of neurology at the University of Kansas and Fellow of the American Academy of Neurology (AAN). The reason is that while researchers followed the rules of good study design by randomly assigning patients to two groups—one taking Axona and one taking placebo—they also added patients toward the end of the study without randomizing them, Dr. Gronseth notes. The addition of these patients could very well have skewed the results.
Randomly assigning patients to treatment groups (for example, by flipping a coin) is an essential feature of good study design because each patient is unique. Without randomization, patients receiving Axona may, on average, be different than patients receiving placebo: They may have more slowly progressing dementia, as an example. This difference, rather than any effect of Axona, might explain why patients taking Axona do better.
“Adding patients without randomization is a frankly bizarre and unscientific way to conduct a study. When the researchers analyzed the results with just the patients who were randomized to the Axona or placebo groups, they found the treatment had no effect,” Dr. Gronseth says. “That's not to say that if people keep doing these studies they may find that medical foods such as Axona actually work, but properly performed research needs to be done.”
Dr. Thies says that in order to help patients and doctors make better decisions, medical food companies should voluntarily commit to doing the same amount of research that they would need to submit if they were seeking drug approval.
Raj C. Shah, M.D., associate professor of family medicine and medical director of the Rush Memory Clinic at the Rush Alzheimer's Disease Center in Chicago, IL, says that patients, advocacy groups, researchers, regulators, and companies should come together to determine what the appropriate pathway is for developing medical foods.
“Currently, there is not a significant demand for the FDA to alter the regulations for bringing medical foods to market,” says Dr. Shah, who has consulted for Accera and has written a review paper on medical foods.
Representatives of Accera say the company is trying to produce better evidence. Holger Kunze, CEO, tells Neurology Now that the company hopes to enroll about 500 patients from 50 to 60 sites throughout the United States for a clinical trial that will test Axona's effectiveness. The trial is set to launch in a few months, he says, but enrollment has not yet begun.
For the time being, is Axona, which sells for approximately $75 for a month's supply and isn't covered by insurance, worth the money?
Probably not, says Nikos Scarmeas, M.D., associate professor of neurology at Columbia University Medical Center. “There are some hints of efficacy, but the appropriate thresholds—those used for FDA medication approval—need to be reached in order to have high certainty about efficacy,” he says.
Dr. Isaacson, who treated Martini's father, says he has seen firsthand how patients can improve on Axona. “As long as it's safe and grounded in scientific evidence, and patients are doing better on it, then I'm ok with that,” he says.
Dr. Thies offers this common-sense approach: “If you can afford the product and it makes you feel better, there is probably little chance of harm in trying it,” he says. “If, on the other hand, you're deciding between buying a medical food or a pharmaceutical drug, the evidence is in favor of buying the drug.”