An FDA advisory committee on Friday voted not to recommend Novo Nordisk’s once-weekly insulin injection in type 1 diabetes patients.
Novo has pitched its candidate as a more convenient alternative to daily insulin doses, including its product Tresiba. But committee members in a 7-4 vote said that the benefits of the insulin, called isodec, did not outweigh the risks in type 1 diabetes patients, who produce little to no insulin.
The majority raised concerns over higher rates of low blood sugar, or hypoglycemia, among patients who took the insulin in a phase 3 clinical trial compared to patients who received Tresiba. The FDA, which is slated to make a final decision in July, does not have to follow the expert panel’s advice, though it often does.
“There are some theoretical benefits, but I think there needs to be more work done targeting. What is the population that could benefit and how do we mitigate the risks of hypoglycemia?” said Albert Einstein College of Medicine professor Jill Crandall, who voted against.
Crandall added that the benefits appear “very clear” in type 2 diabetes patients, though Friday’s advisory committee focused on type 1 patients. The FDA will consider icodec for approval in both type 2 and type 1 patients.
Icodec has already been approved to treat both forms of diabetes in Canada, Switzerland and the European Union.
Novo proposed a number of solutions to prevent hypoglycemic events, including restricting icodec’s use to patients who wear a continuous glucose monitoring device or reducing patients’ meal-time insulin doses when icodec reaches its peak glucose-lowering effect.
Advisory committee members who voted in favor of icodec’s use stressed the need for guidance for physicians and patients.
“If it is approved, there should be a dedicated effort, obviously, for both direct-to-consumer and physician education on insulin dose adjustment and strategies to mitigate that risk,” said Duke University Medical Center Professor Thomas Weber, who voted yes.
Others asked for more data.
“I’m pretty optimistic that there’s a way forward for this once-a-week treatment in type 1, but I think there just needs to be another study in the right population, that shows that the risk of hypoglycemia can be managed in that right population,” NIH statistician Erica Brittain said.
Novo representatives told advisors on Friday that hypoglycemic episodes in the icodec arm were manageable using “the same instructions and methods” as Tresiba. The company also touted the potential adherence benefits of a once-weekly dosing. About 22% of type 1 diabetes patients miss at least one basal insulin dose over any two-week period, which can lead to poor glycemic control, according to the FDA.
“For decades, innovation in insulin development has been guided by the need to reduce patient burden and the frequency of insulin injections,” Shawn Hoskin, Novo’s executive director of regulatory affairs, said during the meeting.
“Novo Nordisk has confidence in the potential of investigational once-weekly basal insulin icodec for those living with diabetes who require basal insulin therapy,” the company said in a statement to Endpoints News on Friday afternoon. “We will continue to work closely with FDA to identify the next steps needed to help provide this novel treatment option for adults living with diabetes.”
Eli Lilly is also working on a rival weekly basal insulin product called insulin efsitora alfa. Earlier this month, the company announced that its candidate efsitora also proved noninferior to Tresiba at reducing A1C levels – which is considered the benchmark of whether a diabetic’s blood sugar is under control – over 52 weeks. Lilly in a statement said that “estimated combined rates of severe or clinically significant hypoglycemic events per patient-year of exposure” were slightly higher in the efsitora arm, but not statistically significant.
The company is expecting topline readouts from three Phase 3 trials this year, which will “complete the submission package for global regulatory review,” a Lilly spokesperson told Endpoints on Friday.