LISBON, Portugal—Drugmaker after drugmaker has been rolling out data on their next-gen meds that lower hypoglycemia risks here at the European Association for the Study of Diabetes meeting, and Friday’s centerpiece unveiling shows why.
Type 2 diabetes patients who suffer episodes of severe hypoglycemia are four times more likely to die within 15 days afterward—and two-and-a-half times more likely to die, period. That’s according to new analyses of Novo Nordisk’s Devote trial, which pitted the Danish drugmaker’s longer-acting basal insulin Tresiba against Sanofi’s long-dominant therapy, Lantus.
Plus, daily fluctuations in blood sugar levels in Type 2 diabetes patients are also associated with a higher risk of death, the analyses found.
The Devote trial itself, rather than after-the-fact analyses, showed that Tresiba cut the rate of severe hypoglycemia by 40% compared with Lantus, and the Novo drug reduced the rate of nighttime hypoglycemia by 53%. Novo has submitted that data to the FDA, hoping for a label change that would illustrate the med’s ability to reduce the rates of hypoglycemia.
"Hypoglycemia is a major problem," Alan Moses, Novo SVP and chief medical officer, said Thursday. "Severe hypoglycemia patients end up in the ER or in the hospital. "We were gratified to see a major reduction in risk of severe hypoglycemia, both over 24 hours and more so at night."
It’s this sort of labeling language that diabetes drugmakers are working toward in delving into comparisons among hypoglycemia numbers put up by drugs used in their trials. Hypoglycemia is dangerous—as this study makes obvious—and costly, because it’s the top driver of emergency room visits in the U.S. Lower hypo numbers can help diabetes meds stand out from their competitors with patients, physicians and payers.
And the basal insulin market is increasingly competitive, what with new products such as Tresiba and Sanofi’s longer-acting insulin Toujeo, not to mention a biosimilar of Lantus launched by Eli Lilly and Boehringer Ingelheim late last year. More is on the way; Merck & Co. has its own FDA-approved Lantus biosim working toward launch. Tresiba brought in 2.1 billion Danish kroner, or about $657 million, in 2016 after its January rollout.
That’s where this Devote analysis fits into Novo’s Tresiba strategy. “Conducting Devote allowed us to do two double-blind trials to specifically assess severe hypoglycemia,” Moses said. An independent committee verified all severe events, without knowing which drug was involved, he explained. The data are about as pristine as you can get for hypoglycemia, he added.
Primarily designed as a cardiovascular outcomes trial, Devote encompassed more than 7,600 participants, and they were at high risk of cardiovascular disease. Over the course of the event-driven study, enough patients suffered severe hypoglycemia to provide a clear picture of the death risks associated with those episodes.
The link between hypoglycemia and death risk “may just be a marker of frailty in the population, but the association is very clear,” Moses said.
Another trial, Switch 2, was directed specifically at hypoglycemia risks, and it found a 51% reduction in severe hypoglycemia episodes among Tresiba patients over the course of the study. At night, the rate for Tresiba patients was 42% lower.
“Our hope, of course, is that hypoglycemia will be added to the label,” Moses said.
Devote was “close to a real-world study,” Moses said, because follow-up was limited to physicians and patients’ own initiative, rather than forced visits. Based on prior research, and machine learning applied to data from Devote and another Novo trial, Leader, the company has come up with a hypoglycemia risk tool to identify patients at high risk of those events.
Devote is the trial Novo mounted after the FDA stiff-armed Tresiba in early 2013, asking for proof of the product’s cardiovascular safety. The request was unprecedented at the time, but signaled a new wave of CV tests for diabetes drugs as the agency, spooked by heart safety questions that had grown around GlaxoSmithKline’s drug Avandia, became more wary of pushing diabetes approvals through without that info. Tresiba was approved in 2015 on the basis of interim data, and full results were released last November. Novo has been mining it for new information since.
The new analyses fit right into one overall theme at EASD. Sanofi rolled out hypoglycemia numbers on its Tresiba rival Toujeo, showing fewer episodes for Toujeo compared with Lantus, this time in Type 1 patients. Those results were collected from patients using continuous glucose monitoring, so blood sugar levels were generated all day long, and the med not only showed it cut the rate of hypoglycemic events but extended the time patients spent in a target blood sugar zone.