PLAINSBORO, N.J.—Glucagon-like peptide-1 (GLP-1) receptor agonists are not new to the world of diabetes treatment but, like so many other diabetes drugs, the route of administration is injection, which is not the most desirable method for most people who need to take a medication regularly to manage a chronic condition. And so, in what will likely be a sigh of relief for many patients with type 2 diabetes (T2D), Novo Nordisk recently announced that it had gained approval from the U.S. Food and Drug Administration (FDA) for an oral option—a pill—for semaglutide, marketed under the name Rybelsus. Better yet, for those many patients who dread having to keep track of multiple pill regimens multiple times a day, the drug is a once-daily formulation.
Novo Nordisk has been in the diabetes business a very long time, so going in a direction like this is not surprising. As the company notes on its website, “Novo Nordisk scientists are currently refining the treatment of type 2 diabetes—for example, by advancing from subcutaneous injections to oral administration. Our research focus has also expanded from only reducing blood glucose levels, to also treating related complications.”
What the FDA approved were Rybelsus tablets in both 7 mg and 14 mg dosages that, along with diet and exercise. may improve blood sugar. Rybelsus is the first and so far only GLP-1 analog in a pill, marking a likely welcome new option for adults with T2D who are not achieving their hemoglobin A1C blood level goals with current antidiabetic treatment.
Share prices for the company rose by 3 percent shortly after the announcement.
The approval of Rybelsus is based on results from 10 PIONEER clinical trials, which enrolled 9,543 participants and included head-to-head studies of Rybelsus vs. sitagliptin, empagliflozin and liraglutide 1.8 mg. In the trials, Rybelsus reduced A1C and, as a secondary endpoint, showed reductions in body weight. The most common adverse reactions in the PIONEER trials, reported in around 5 percent of patients, were nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation. The types and frequency of the adverse reactions were similar across trials.
“GLP-1 receptor agonists are effective medications for people with type 2 diabetes, but have been underutilized in part because they have, until now, only been available as an injectable treatment,” said Dr. Vanita R. Aroda, director of the Diabetes Clinical Research program at Brigham and Women’s Hospital in Boston and a PIONEER clinical trial investigator. “The availability of an oral GLP-1 receptor agonist represents a significant development and primary care providers, specialists and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals.”
“People living with type 2 diabetes deserve more innovation, research and support to help them achieve their individual A1C goals,” added Todd Hobbs, vice president and U.S. chief medical officer of Novo Nordisk. “With Rybelsus, we have the opportunity to expand use of effective GLP-1 receptor agonist therapy by providing adults with type 2 diabetes an oral medication which was previously only available as an injection to help with managing their blood sugar.”
Rybelsus is approved for once-daily use in two therapeutic doses, 7 mg and 14 mg, and will be available in the United States beginning in the fourth quarter of this year. Initial supply of Rybelsus will come from manufacturing facilities in Denmark; however, future supply for Rybelsus will come from U.S. manufacturing facilities, which is largely made possible by a 2015 move by Novo Nordisk in which it made a strategic investment to build a new manufacturing facility in Clayton, N.C., to prepare for the future demand for Rybelsus. Additionally, earlier this year Novo Nordisk acquired a tableting and packaging facility in Durham, N.C., to meet anticipated supply needs for Rybelsus.
The U.S. FDA is still reviewing Novo Nordisk’s new drug application (NDA) for Rybelsus seeking an additional indication to reduce the risk of major adverse cardiovascular events such as heart attack, stroke, or cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. A decision is expected in the first quarter of 2020.
Rybelsus is currently under review by several regulatory agencies around the world, including the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency.