The prevalence of diabetes has reached epidemic proportions in both the U.S., where 9.3% of the population has diabetes, and in the world at large, where 8.3%—roughly 387 million people—have diabetes. And it’s only getting worse. The Centers for Disease Control and Prevention (CDC) predict that by 2050, one in three people in the U.S. will be living with diabetes, which means that they have a good chance of dying prematurely from a diabetes-related complication.
Diabetes, the seventh leading cause of death in the U.S., is the cause of a great deal of suffering, including blindness, neuropathies, pain, lost limbs, heart attacks, disability, and the constant stress of having to manage a disease that demands constant and precise blood-glucose (BG) management.
Clearly, there continues to be a need for innovation in diabetes therapeutics. And according to Dr. Todd Hobbs, VP and Chief Medical Officer at Novo Nordisk, large-scale, game-changing innovation is indeed underway.
Hobbs’ perspective on what it means to be innovative in this space is driven by real-world experience, including ten years of clinical practice treating patients with diabetes, more than 10 years of experience at Novo and, on a personal level, the fact that both he and one of his young sons has type 1 diabetes (T1DM).
Using genomics to drive innovation in type 1 diabetes
According to a report from the Pharmaceutical Researchers and Manufacturers of America (PhRMA), there are 182 drugs in development for diabetes, including 30 therapies for T1DM. Although there are fewer drugs in development for T1DM compared with type 2 diabetes (T2DM), according to Hobbs, a lot of progress is being made in this area.
"There has been a lot of work focused on defining the genomic makeup of type 1 diabetes, which has allowed researchers to identify biomarkers that could help determine whether a patient will respond to a specific therapy," he told BioPharma Dive in an interview. "I consider this approach radically innovative."
In addition, Hobbs is optimistic about the progress that’s been made in developing a closed-loop system. In diabetes, a closed-loop system is an automated mechanical glucose-responsive, sensor-guided insulin- infusion system. His prediction: “Within three to four years we will see a closed-loop system. Right now, we have the sensors and insulin pumps, and these are being combined along with algorithms to more precisely control insulin delivery to the patient. Ultimately, the goal is to provide this type of system for patients with type 1 diabetes via a wearable device that requires minimal input from the patient.”
Type 2 diabetes: Turning injectables into oral treatments
Hobbs views T2DM as more challenging than T1DM, especially in terms of being able to isolate genetic markers. The main challenge is that T2DM is more complex and heterozygous than T1DM. In fact, Hobbs concedes that the chances of finding a radical cure for T2DM will probably not happen during our lifetimes. Nonetheless, T2DM is where some of the most innovative, paradigm-shifting research and development is taking place—and a lot of it is happening right in Novo’s labs.
Novo is one of two companies working on development of an oral insulin product (Oramed is also at work on a similar therapy). The company's oral insulin is still in phase I, but Hobbs expects it to advance to phase II later this year.
"Oral insulin has always been the holy grail of diabetes drug development, because no one likes injections," he said. "Also, there are millions of patients with T2DM who fear insulin, because of the risk of hypoglycemia. A once-a-day insulin pill would be a radical change for the type 2 market. However, I don’t think we will ever have the precision with an oral insulin pill that we have with injectable insulins. The advantage of injectable insulin is that it allows patients to manage the hour-by-hour changes that are part of the daily life of people with diabetes."
Oral insulin is a big deal, but Novo has another oral product in development, OG217SC (semaglutide), that has the potential to shift the entire T2DM treatment paradigm. "We are developing the first non-injectable GLP-1 agonist, which has all of the attributes associated with this class—glucose-dependent insulin release, improved weight management and effective BG management—with essentially zero risk for hypoglycemia," Hobbs said.
Compelling phase IIa data for Novo’s oral peptide therapy
In a 26-week, placebo-controlled study of oral semaglutide, 600 patients with T2DM were randomized to either oral semaglutide or placebo. Patients who were treated with semaglutide received one of five different doses ranging from 2.5 mg to 40 mg. Semaglutide-treated patients achieved statistically significant dose-dependent improvements in HBA1c (from a mean baseline HBA1c of 7.9%) of 0.7% to 1.9% after 26 weeks, compared with improvements of 0.3% in placebo-treated patients. Overall, all doses of oral semaglutide were statistically superior to placebo.
In addition, patients treated with the highest doses of oral semaglutide had an average weight loss of 14 pounds (from a mean baseline of 203 pounds), compared with slightly more than two pounds for placebo-treated patients. Also, semaglutide demonstrated a good safety and tolerability profile in this study.
As Novo moves towards phase III with oral semaglutide, the medical community is hopeful about the prospect of being able to achieve such powerful results with an oral peptide. "Approval of oral semaglutide would be a tremendous innovation," Hobbs asserted.
The role of technology in personalizing diabetes treatment
When Hobbs steps back and looks at the big picture, he boils innovation down to one major factor—technology. "Technology is the game-changer of the 21st century," he said. "The biopharma industry is just starting to partner with the Googles of the world now that these companies have realized that personalized medicine is such an exciting field that they want to be part of it."
There are many examples of technology driving improvements in diabetes care and management, including numerous types of monitoring devices, as well as applications that provide patients with personalized feedback and support.
Novo Nordisk has been at the forefront of innovation in diabetes therapeutics since 1923 when it was founded. In 2014, Novo led the diabetes market, with a total of $11.3 billion in diabetes-related sales. That success is continuing, with recently reported second-quarter sales up 19% quarter over quarter, and full-year expectations for 2015 that have been revised upwards.
Despite all of the good news, Hobbs is concerned about the challenge of determining which endpoints are most meaningful when it comes to diabetes-related outcomes in clinical trials. "There is no consensus on the meaningful endpoints that payers can agree on," he said. "We can focus on adherence to therapy or patient-reported outcomes, as well as clinical metrics, but ultimately patients know what works for them."
The idea that one in three people in the U.S. will have diabetes within 35 years seems far-fetched, but given the current trajectory, those statistics could become a reality. During the next 35 years, Novo and other companies working in this space will continue to leverage technology to improve disease-state management, and in the process, improve long-term outcomes for patients with diabetes.
"There is still a lot of work to do," said Hobbs.