Summary: Axona is Accera’s new product for people with mild to moderate Alzheimer’s. Available in the U.S. by prescription only, Axona is marketed as a medical food. This means it was not subject to FDA pre-market review and approval. Results of the company’s trials of Axona sound promising, but we’ll have to wait for more data to be published to get a better idea how effective the product is.
Suddenly, Axona is everywhere. I heard people talking about it at a local Alzheimer’s educational event last week. There’s an advertisement for it on the back cover of the latest edition of the Alzheimer’s Foundation of America’s magazine, care ADvantage. Accera, the company that developed Axona, is also a silver sponsor of the Alzheimer’s Association’s upcoming ICAD conference.
Axona is designed to address the “hypometabolism,” or reduced use of glucose, seen in some areas of the brains of people with Alzheimer’s. Glucose is the brain’s source of energy. Axona is formulated as a powder, and is mixed with water to make a once-a-day drink.
The product is unique in its approach to Alzheimer’s and in Accera's choice to market it as a “medical food.” I talked last week with Steve Orndorff, Ph.D., founder and CEO of Accera, to get more details.
Accera markets Axona as a medical food, available only by prescription. Medical foods do not require the same U.S. Food and Drug Administration (FDA) review and approval as drugs. Without the lengthy FDA review, if no data from placebo-controlled trials is published in peer-reviewed journals, it can be difficult to assess how effective a medical food is.
Medical foods are subject to some FDA oversight and regulation, which can include monitoring manufacturing processes and quality assurance programs, and analyzing ingredients for safety. The agency does not necessarily conduct inspections for all medical foods, though. In addition, food ingredients must be “Generally Recognized as Safe” (GRAS) to be exempt from pre-market review and approval. [Outside experts file notices with the FDA about evidence that food ingredients are safe; the agency does not affirm these claims.] Dr. Orndorff says the ingredients of Axona are all in the FDA’s database of notices about GRAS ingredients, and that people should feel confident that the product won’t have any serious adverse effects.
Why did Accera choose to market Axona as a medical food rather than as an FDA-approved drug? Developing a potential drug, conducting clinical trials and going through FDA review is a lengthy and expensive process, but Dr. Orndorff says that’s what Accera had planned to do. In fact, the company completed some Phase 2 trials (see below).
“We wanted to go the prescription drug route,” he says. “We were using it [the Axona formula] as a surrogate to see if the whole approach would work. We were going to ask investors for funding to develop a drug based on this approach. But the results were so compelling, we thought it was unethical to sit on this – let’s go to market, we said.”
And why not market Axona as a “nutraceutical,” which would be available without prescription? Accera’s management decided that the medical foods category is more attractive from a business perspective. “We can make a disease claim if it’s marketed as a medical food,” says Dr. Orndorff. “If it were a nutraceutical, we could only say it ‘supports brain health,’ and it might not get into the hands of patients and physicians because the product would have low awareness.”
I asked the Alzheimer’s Association to comment on Axona’s characterization as a medical food. Their public relations personnel referred me to a March 2009 statement from their Medical and Advisory Council which says medical foods are a “subject of concern” because without pre-market FDA approval, the Association cannot be sure about the scientific scrutiny any evidence has undergone. This statement refers to medical foods in general, and does not mention Axona.
The science behind Axona
Researchers have been exploring the link between hypometabolism and Alzheimer’s for more than 25 years, but don’t yet fully understand it. Some studies have shown that giving glucose (or the insulin that helps the body process glucose), to people with Alzheimer’s improves their memory. More research is needed, and it may not be practical or healthy to increase levels of either glucose or insulin over a long period.
The theory behind Axona is that if brain cells aren’t getting or using enough glucose, you can substitute ketone bodies for glucose. A ketone body is a substance that results from fats being broken down in the body. The amount of ketone bodies circulating in the blood can be increased by a diet extremely high in fat and extremely low in sugar. Although this diet is difficult to stay on, it is used to treat seizures in some cases.
The main ingredient of Axona, caprylic acid, causes an increase in ketone bodies in the blood without the need for a high fat diet. So at least in theory, Axona provides an alternate fuel for brain cells.
Caprylic acid is found in coconut oil, and there have been anecdotal reports of that oil improving memory, including a story in my local newspaper. But coconut oil is very high in saturated fat, and might cause health problems in some people, Dr. Orndorff says.
Accera has completed Phase 2 trials of Axona for both mild to moderate Alzheimer’s and for “age-associated memory impairment,” but most of this data is not available for review right now. Dr. Orndorff says that for the Alzheimer’s trial data that is in the public domain, however, participants without the APOE4 genetic variation taking Axona showed more improvement on the ADAS-Cog test than a large analysis of multiple trials showed for Aricept. He expects data from the Alzheimer’s trial to be published in a medical journal in six to eight weeks.
Recent trials of other Alzheimer’s drugs have also shown different results for people with APOE4 than for people without the genetic variation. In the past, trials weren’t designed to test effectiveness for subsets of participants, and so the numbers of people in the subset groups haven’t been big enough for those subset results to be statistically valid. Without more detailed data, I can’t tell if this is the case for the Axona trials. Many new trials are being designed with these genetic subsets in mind.
The company has no immediate plans to conduct larger Phase 3 trials, but is planning to follow up with a study at Duke University to further test how effective the product is. This study will also test whether functional MRI imaging can detect changes in the metabolism in the brains of people taking Axona.
Axona is available by prescription, in the U.S. only, and the cost for a month’s supply ranges from $83 to $110 ($99 at my local pharmacy). The product is not covered by most insurance plans or by Medicare, but is reimbursed as part of TRICARE military health benefits, says Dr. Orndorff.
Accera is not recommending that doctors order APOE genetic testing before prescribing Axona, partly because of doctors’ concerns about ethical issues involved in gene testing, he says. And although available data shows that people with the APOE4 genetic variation did not respond as well to Axona during the trial period, they seemed to stabilize (as opposed to the expected decline) during a nine month open label extension of the trial, according to Dr. Orndorff.
During the trial, some participants experienced diarrhea or indigestion. The information for professionals on the Axona site recommends that the product be taken with food, and any digestive problems managed with over-the-counter medications. If problems continue, the company recommends temporarily cutting the dosage in half.