The FDA is raising concerns about increased rates of hypoglycemia following treatment with Novo Nordisk’s experimental once-weekly basal insulin ahead of an advisory committee meeting on Friday.
In briefing documents published Wednesday, regulators noted higher rates of hypoglycemia among patients who took Novo’s once-weekly insulin icodec compared to those who took daily insulin degludec, also known as Novo’s Tresiba.
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee will meet Friday to vote on whether insulin icodec’s benefits outweigh its risks for improving glycemic control in adults with type 1 diabetes.
Type 1 diabetes is characterized by high blood sugar. While insulin products are often used in multiple daily doses to lower a patient’s blood sugar, problems can arise if their blood sugar drops too low, the condition known as hypoglycemia.
Novo has touted insulin icodec as a more convenient option than daily basal insulins, which are associated with poor adherence. About 22% of type 1 diabetes patients miss at least one basal insulin dose over any two-week period, the FDA said Wednesday. In its own briefing documents, Novo tied low adherence to “a spiral of negative consequences,” including increased hospitalization and mortality.
Hypoglycemia is a known side effect of insulin therapy. But regulators noted that Novo’s Phase 3 trial results showed “excess hypoglycemia caused by insulin icodec (versus the active comparator) without evidence of any additional glycemic control or other benefit.” The FDA added that insulin degludec may be associated with less hypoglycemia risk compared to other competing insulin products.
Novo argued in its briefing documents that the risk can be “effectively managed by guidance provided from physicians.”
“Severe hypoglycemic episodes (level 3) occurred in similar proportion of participants between the two treatment arms and the higher rates in the insulin icodec arm are mostly due to 1 participant experiencing 70% of the episodes. In both treatment arms the severe hypoglycemia episodes were of similar duration and managed and resolved in the same way,” the company said.
Novo proposed a number of solutions to prevent hypoglycemic events, including restricting insulin icodec’s use to patients who wear a continuous glucose monitoring device and who have lower glycemic variability, which was associated with lower hypoglycemic risk in a subgroup analysis. The company also suggested reducing patients’ bolus (meal-time) insulin doses between days 2 and 4 after each weekly basal injection, when insulin icodec reaches its peak glucose-lowering effect.
But FDA reviewers were skeptical.
“However, no clinical data are available to assess the impact of these proposed risk mitigation strategies (or confirm that a reduced risk of hypoglycemia can be achieved without decreasing efficacy),” they wrote.
The FDA extended its review of insulin icodec by three months because of new data that constituted a “major amendment,” according to Novo. The drug’s PDUFA date is in July. Meanwhile, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended an approval in March.
“Novo Nordisk remains confident in the potential of once-weekly insulin icodec to help those living with diabetes needing insulin. We continue to work closely with the FDA as it completes the reviews needed to bring this important medicine to the diabetes community,” a Novo spokesperson said on Wednesday.