Company Looks to Enhance Pharmaceutical Effectiveness While Lowering Dosages
In the last few months, Nashville-based NuSirt Biopharma has initiated its first clinical trial in humans, completed one of the year’s most successful capital campaigns, and presented two papers at the American Diabetes Association’s 74th Scientific Sessions. NuSirt also holds two patents and has 13 active patent applications under review for its proprietary technology platform … not bad for a company that hasn’t even celebrated its first decade in business, yet.
Incorporated in 2010 by Michael Zemel, PhD, who has authored more than 200 peer-reviewed articles primarily focused on metabolic regulation, NuSirt’s technology combines the essential amino acid leucine with existing human medications that target diabetes, obesity and other metabolic diseases. Zemel served as a professor of Nutrition and Medicine and director of the Nutrition Institute at the University of Tennessee for more than two decades. The company’s chief scientific officer left his academic post in 2012 to focus his full efforts on growing NuSirt’s technology and applications.
On the business side, Joe C. Cook, Jr., a veteran pharmaceutical industry executive, leads NuSirt in his role as president and executive chairman of the board. After retiring from Eli Lilly in 1993, Cook led a small biotech company for the next 10 years. Upon ‘retiring’ again, he returned to his native Tennessee where he was introduced to Zemel’s research.
“All of his work was focused on the components of nutrition that affected energy and metabolism,” Cook explained, adding the science was similar to other research he had seen throughout his pharma career. However, Zemel’s work focused on leucine and took a different approach by honing in on fat cells.
“Of all the amino acids he had studied, leucine was the only one that really promoted efficiency in animals and humans handling energy,” Cook said. “A gram of protein has four calories; a gram of carbohydrate has four calories; but a gram of fat has nine calories,” he continued. “On a mass-to-mass basis, the body’s most efficient storage mechanism is a fat cell.”
Cook said the data was convincing that Zemel’s methodology could positively impact cellular activity by adding a specific amount of the branched chain amino acid leucine to amplify metabolism. A principal and co-founder of Nashville-based Mountain Group Capital, Cook decided to invest in the fledgling company that had the potential to improve the treatment of obesity and type 2 diabetes.
“Diabetes is growing in the United States at a rate greater than our population,” Cook said. “That kind of epidemiology clearly illustrates that we haven’t solved the problem.”
He added the multifactorial nature of most metabolic conditions and resulting impact on body systems has made it difficult to create a cure. However, he believed Zemel’s approach offered a way to achieve much better glucose control by enhancing the effectiveness of the existing pharmaceutical metformin.
Less is More
Metformin is used by millions of Americans as the recommended first-line oral treatment for type 2 diabetes if control cannot be achieved through diet and exercise alone. “Metformin is the most widely prescribed medicine for diabetes in the world,” Cook stated.
Although quite effective and with fewer issues than other glucose control medications, the popular drug still comes with a significant profile of side effects, typically manifesting as gastrointestinal distress. “It’s always been my experience that almost every drug has side effects and almost always it’s associated with the quantity of drug needed,” Cook noted.
He continued, “The literature has shown between 30-50 percent of people who take metformin experience some GI distress from mild to major. A much smaller percentage … estimated between 6-10 percent … suffer more serious adverse events with metformin to the point where they take it less frequently, lower the dose, or stop taking it altogether.”
NuSirt’s working theory was to utilize leucine to amplify the effect of metformin thereby allowing for lower, more tolerable dosing levels. The theory was borne out in animal models resulting in glucose control with a reduction in fatty deposits with a significantly lower dosage of metformin.
“Most drugs activate a signal in the body. They either bind to or block a receptor … you either stimulate a cell or suppress it,” Cook explained. “Leucine works on the sirtuin pathway,” he continued. “It makes that receptor system more sensitive to metformin, and that gives rise to a potentially lower dose. That’s the really novel observation.”
Human Trials Launched
Cook said the success demonstrated in animal models in 2013 led the company to file an investigational new drug (IND) application with the U.S. Food & Drug Administration earlier this year. “In July, the FDA gave us the green light to proceed with our human studies,” he added.
The first randomized, double blinded study is currently active at eight sites, including Vanderbilt and Meharry in Nashville. To reduce any latent effects of the drug, Cook said all participants in the study must come off of their oral diabetes medication for a month prior to beginning the active phase of the trial.
Inclusion criteria include being on only one oral medication for glucose control and having an A1C between 7 and 8.5. “If during the four-week washout period their glucose goes up too much, there is an escape route to get them out of the study and back onto medication,” Cook said of the careful monitoring.
During the 28-day trial, the 100 participants wear a blood sugar monitoring device and measure their blood glucose levels frequently. The control arm of the trial is receiving standard doses of metformin as clinically prescribed compared to the other three arms receiving one of three lower doses of the metformin combined with the NuSirt technology. The goal is to assess the general effectiveness of the combination therapy and find the lowest dose possible to achieve glucose control. Initial results are expected by first quarter 2015. NuSirt plans to substantially increase its clinical trial program leading to the filing of a New Drug Application with the FDA pending positive results from this first clinical trial.
If the success seen in animal models is replicated in humans, it could signal transformational change in how healthcare providers approach and manage glucose control and pave the way for new treatment options for other metabolic conditions.
November is American Diabetes Month
Diabetes is a chronic condition at epidemic proportions in the United States. According to the American Diabetes Association nearly 30 million children and adults in the U.S. have diabetes and another 86 million Americans have pre-diabetes.
Whether or not medication management is required, the ADA stresses everyone with diabetes benefits from healthy lifestyle choices. For 2014, the national organization has adopted the theme, “America Gets CookingSM to Stop Diabetes.” The message this year centers on engaging in improved nutrition and moderate physical activity in a social manner to make it fun to opt for the healthy choice.
For promotional materials and more ideas to share with your patients, go online to diabetes.org and click on “In My Community.”
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