After encouraging results, Accera has found a way to speed its Alzheimer’s disease treatment to market without conducting the late-stage clinical trials required for most drugs. Nor will the privately held company seek U.S. Food and Drug Administration approval—often a lengthy process—to market its product Ketasyn. That’s because rather than treating it as a drug, the Broomfield, Colorado company is treating it as a “medical food,” which eliminates the need for pre-market approval.

Medical foods are not sold through grocery stores, but are available only through a doctor’s prescription. The FDA considers medical food as products that can be used to manage a disease through one’s diet. They must be specially formulated and processed as opposed to naturally occurring. Specifically, they are intended for patients with an impaired capacity to digest, absorb or metabolize ordinary foods or certain nutrients—but only when the condition can be helped by modifying their diet. 

“We have a product with a different mechanism of action than those drugs in the marketplace today,” said Steve Orndorff, president and CEO of Accera, who noted there are no new drugs for Alzheimer’s expected on the market before 2012. “Our ability to get into the marketplace right away and take advantage of that window of opportunity is just huge.”

Founded in 2001, Accera is readying to launch Ketasyn in November. It is in the process of building a sales force of about 25 people and raising a $30-million venture round. Orndorff thinks the company can reach sales of $200 million a year within four years. But the company has been able to reach this milestone with just 12 employees and $12 million in funding in part by treating Ketasyn as a medical food rather than following the longer and more costly road to market of a conventional drug.

Accera argues that Alzheimer’s patients suffer from a metabolic disruption that inhibits the brain’s ability to use glucose to power neurons. Ketasyn is converted by the liver into ketone bodies, which brain cells can use for energy even when their ability to metabolize glucose is impaired. The body naturally breaks down fat into ketone bodies to use for energy when insulin is unavailable.

A New Approach
The approach represents a new one to Alzheimer’s. Existing drugs largely focus on correcting the deficit in the neurotransmitter acetylcholine. Many of the drugs under development for Alzheimer’s focus on preventing the amyloid beta plaque build-up that leads to cognitive impairment in the disease or seek to clear it. 

Other research, though, has highlighted the use of sugar by the brain to make and use energy. Recent research has focused on insulin resistance in the brain in Alzheimer’s patients, with researchers at Brown University in 2005 suggesting that the neurodegenerative disease might be a Type 3 diabetes. By targeting the metabolic defects in Alzheimer’s patients, Ketasyn works in what is believed to be the earliest stages of the disease before signs of impairment become evident.

Glucose is the main fuel that powers the brain, but in Alzheimer’s disease, neurons are unable to effectively metabolize it to generate energy. Unable to produce adequate energy, the brain doesn’t efficiently utilize fats, fails to produce adequate amounts of the neurotransmitter acetylcholine, and can’t properly clear the cellular proteins in the brain that give rise to the telltale plaque associated with the disease.

Ketasyn is a liquid suspension that the company provides with a sweet vanilla flavor. Accera argues that hypometabolism—the inability to utilize glucose—is a dietary insufficiency that is common to Alzheimer’s disease and its product satisfies that need.

 

Leo Kim, a partner with Carlsbad, California-based POSCO BioVentures, an investor in Accera, said while the accelerated path to market is significant for the company, it does not represent a way to bypass the scientific rigor that clinicians and the public demand. “It’s a different route to the consumer.”

A mid-stage clinical trial of 152 patients that had previously been diagnosed with mild to moderate Alzheimer’s disease showed Ketasyn improved memory and other aspects of cognitive performance. The trials used AD Assessment Scale-Cognitive or ADAS-Cog score to measure changes in patients. The trials tested patients with a genetic variation seen in half of Alzheimer’s patients known as ApoE4(-). The population experienced a 3.5-point improvement after twelve weeks compared to the placebo group. ApoE4(-) patients who also exhibited a genetic variation that affects glucose regulation, showed a 5-point improvement in ADAS-Cog scored compared to placebo.

The company said regardless of genotype, subjects who remained on Ketasyn for all nine months of the study showed very little disease progression, declining only 0.8 points below baseline in ADAS-Cog scores in contrast to the 5.4-point decline observed in placebo subjects extrapolated to nine months. Ketasyn in a separate trials has also shown clinical benefit in treating age-associated memory impairment, a possible precursor to Alzheimer’s. The company said clinical trials have shown Ketasyn to have an “excellent” safety profile. The incidence of adverse events was low and similar between Ketasyn and placebo groups.

Accera will continue conducting clinical trials after Ketasyn is on the market. The company is currently conducting a pivotal, late-stage, multi-center clinical trial in mild-to-moderate Alzheimer’s patients. This study focuses on several measures of efficacy, including ADAS-Cog, safety and the role of insulin regulation in Alzheimer’s disease.

In the absence of the rigorous requirement for proving effectiveness to win an FDA approval, though, Alzheimer’s experts are not sure how widely Ketasyn will be adopted. Sam Gandy, chairman of the Alzheimer’s Association Medical and Scientific Advisory Council, said he expects once it’s released, academics will subject it to the type of testing a drug would go through, but it will be difficult to predict how quickly doctors might prescribe it to their patients.

 

“It’s obviously a desperate disease and everyone is looking for anything that will even help a little bit, but since this does not go through the FDA, it’s difficult to know what to expect from it once it gets to market,” he said. The good thing is its safe—these are chemicals that naturally occur in the body.”

 

Accera is also working to develop drugs to treat Parkinson’s disease and Huntington’s disease. These programs are both pre-clinical and are expected to follow a conventional regulatory pathway for drugs, but work with a similar mechanism of action to Ketasyn to provide neurons with an alternative fuel source.

 

But for Accera, it is Ketasyn that will likely determine its future. “The success or failure of the company hinges on the commercialization of this product,” said Orndorff. “We’re guardedly optimistic that there’s going to be a fairly quick market uptake of the product because Alzheimer’s patients and caregivers are desperate for some alternatives. They are a well-informed patient population. They are very aware of new development and very early adopters compared to other disease areas.”