Background

This is a nutritional beverage. Ketasyn/AC-1202 was tested in Phase 1 and 2 safety/dosing trials, but in Phase 2 missed its primary endpoint and was not advanced to Phase 3 efficacy trials. Rather, in 2009 its developer, Accera Inc., since renamed Cerecin, brought it to market as a once-daily medical food called Axona. Medical foods do not undergo pre-market FDA review or approval. Unlike dietary supplements, they are not available over the counter but are prescribed by physicians.

Axona is a proprietary formulation of processed coconut or other oils and glycerin. Its active ingredient is caprylic acid, along with other medium-chain triglycerides. Caprylic acid metabolism in the liver leads to substances called "ketone bodies," which cross the blood-brain barrier. These have been hypothesized to provide an alternative to glucose as the brain's source of energy in conditions marked by impaired neuronal metabolism, such as Alzheimer's. Brain imaging by FDT-PET shows cerebral glucose hypometabolism in regions affected by Alzheimer's. 

Axona's effectiveness has been called into question by experts in the field, e.g. , Oct 2009 news series. As a result of media stories covering the controversy (e.g., ABC News), demand for coconut oil as a cheaper source of caprylic acid rose. However, there is no scientific evidence that it is effective. 

On 26 December 2013, the FDA issued a warning letter charging Accera with 'false and misleading labeling.' Ketasyn, the FDA elaborated, does not meet the statutory definition of a medical food, but is instead an unapproved drug (see FDA 2013 Warning Letters). In May 2014, Accera was subject to a related class action lawsuit before the 11th Judicial Circuit court in Florida (see Law360 story).

The company is testing other formulations of caprylic acid triglyceride for possible FDA approval (see Tricaprilin).

In October 2018, Accera re-branded itself as Cerecin, following investments from a Singapore-based agribusiness group and a private equity fund backed by Nestlé (press release).  The company plans to market Axona in Asia-Pacific countries.

Findings

A two-week open-label safety, tolerability, and pharmacokinetics study of different formulations of Ketasyn in 60 healthy elderly volunteers preceded two Phase 2 studies.

From 2004 to 2006, a 90-day, double-blind, multicenter trial in 152 patients with mild to moderate Alzheimer's disease evaluated Ketasyn against the Alzheimer's Disease Assessment Scale—cognitive subscale (ADAS-cog), the Alzheimer's Disease Cooperative Study—Clinician's Global Impression of Change (ADCS-CGIC), and the Mini-Mental State Exam (MMSE). This trial was reported to have improved cognitive function in participants on Ketasyn at the 45-day trial mid-point, though the difference was no longer statistically significant by 90 days. In ApoE4 non-carriers, the effect did remain statistically significant by 90 days. Adverse event discontinuations were 23 percent, mostly for diarrhea, flatulence, and dyspepsia (Henderson et al., 2009).

From 2006 to 2007, a second 90-day trial in 150 older adults with "normal" loss of memory abilities since early adult life evaluated Ketasyn. This trial used changes in the Psychologix and Cogscreen Test Batteries, RAVLT (Rey Auditory Verbal Learning Test), as primary outcome. The results were not published. 

In 2010, Accera started a PET study at the University of California, Los Angeles, to evaluate the effects of Axona on cerebral metabolism in 22 participants with Alzheimer's disease. This trial measures regional cerebral blood flow in response to 45 days treatment with Ketasyn, comparing ApoE4 carriers to non-carriers. According to published results, participants lacking an E4 allele showed an increase in regional blood flow in parts of the cortex and the cerebellum and hypothalamus, while ApoE4 carriers did not (Torosyan et al., 2018).

For all clinical trials on Ketasyn, see clinicaltrials.gov.