Diabetics know all too well that needle sticks are a routine part of managing their disease. Insulin injections have been part of the diabetes standard of care for decades. And in recent years, a new class of injectable drugs have emerged to help patients regulate their blood sugar levels.
Chapel Hill, NC, drug developer BioKier is beginning human tests of a drug that, if successful, could replace these injection therapies with a pill that coaxes the body to regulate blood sugar levels on its own, says George Szewczyk, BioKier founder and CEO. If it works, BioKier’s approach could offer some advantages over blockbuster diabetes drugs currently available from big pharmaceutical companies.
“We believe we have a better safety profile,” Szewczyk says. “We also believe that there is a very good chance that our drug will be more efficacious than other drugs.”
The inspiration for BioKier’s lofty goal comes from an unlikely origin: gastric bypass surgery.
Patients who have undergone a gastric bypass lose weight in part because shrinking the stomach’s size reduces the amount of food needed to make a person feel full, so patients eat less. But researchers observed another beneficial effect, says Roger Nolan, BioKier co-founder, president, and chief operating officer. The blood sugar of many diabetics returned to normal levels shortly after the surgery. In some cases, diabetes simply went away.
Research linked this effect to a gut hormone that regulates blood sugar. Secretion of this hormone, called a glucagon-like peptide-1, or GLP-1, is triggered by nutrients from food, Nolan explains. Because it leaves patients with a tiny stomach, gastric bypass surgery results in those nutrients being digested further along the digestive tract, at the beginning of the colon, which prompts the body to release GLP-1. BioKier’s experimental drug, for now called BKR-013, aims to mimic this effect with a pill that carries a payload of the nutrient glutamine into the colon. Nolan calls it “gastric bypass in a pill.”
The global market for diabetes treatments is in the tens of billions of dollars. BioKier is far from the first pharma company to take a GLP-1-based approach to treating the disease. Novo Nordisk’s (NYSE: [[ticker:NVO]]) Victoza (liraglutide), for instance, is an analog drug, meaning that it is similar to GLP-1. The once-daily injectable generates more than $2.1 billion in annual sales. Byetta (exenatide), a twice-daily injectable GLP-1 analog originally developed by San Diego biotech Amylin Pharmaceuticals and now marketed by AstraZeneca (NYSE: [[ticker:AZN]]), generated $206 million in 2013 sales. A once-weekly version of that drug, Bydureon, produced $151 million in sales last year for AstraZeneca. And Eli Lilly (NYSE: [[ticker:LLY]]) is awaiting the Food and Drug Administration’s decision on dulaglutide, which is expected to take market share from liraglutide.
While GLP-1-like drugs help diabetics reduce their glucose levels, these drugs have also been linked in animal tests, clinical trials, and post-marketing studies with possible higher risks of pancreatitis and cancer. Szewczyk says that GLP-1 produced in the body has a short half-life, meaning it will disappear soon after a meal. Consequently, he says, stimulating production of the hormone with BioKier’s drug shouldn’t pose the health risks associated with treatments like liraglutide and exenatide that introduce longer-lived analogs of GLP-1 into the body.
At least one other company has explored an approach similar to BioKier’s. Lumena Pharmaceuticals, a San Diego company that was acquired for $260 million earlier this year by Shire Pharmaceuticals (NASDAQ [[ticker:SHPG]]), tried using bile acids, rather than glutamine to trigger GLP-1 production. But prior to the Shire acquisition, Lumena, which was launched in North Carolina in 2011 with early investment from Durham venture capital firm Pappas Ventures, had shifted its research focus away from diabetes; Lumena instead turned toward rare liver diseases.
BioKier’s technology stems from more than Szewczyk’s research—it also comes from his own experience with diabetes. In 20 years at GlaxoSmithKline (NYSE: [[ticker:GSK]]) and its predecessor companies, Szewczyk researched treatments for diabetes and obesity. But he says it wasn’t until he left GSK in 2008 that he developed the disease himself.
Szewczyk had read studies on the research of non-digestible sugars as a diabetes treatment, research that had been conducted in rats. He decided to test whether one of these sugars, lactitol, would help control his diabetes. The experiment was a success, and with continued treatment he shows no diabetes symptoms. “My diabetes fully reversed and is fully in control,” Szewczyk now says.
At about the time of Szewczyk’s initial test, he came upon research from Fiona Gribble at the Cambridge Institute for Medical Research. He was intrigued by Gribble’s research on glutamine as a trigger for
