The FDA’s Complete Response Letter turned down Novo Nordisk’s Biologics License Application for its once-weekly basal insulin icodec injection for diabetes mellitus, with “requests” related to the manufacturing process and the type 1 diabetes indication.
The FDA on Wednesday denied approval for Novo Nordisk’s once-weekly basal insulin icodec injection for the treatment of diabetes mellitus.
In its Complete Response Letter, the regulator made “requests” related to the drug candidate’s manufacturing process, Novo said in its announcement. The FDA also raised concerns related to the use of insulin icodec in type 1 diabetes (T1D). Novo does not expect to be able to respond to these requests this year.
The Danish pharma will continue to “work closely with the FDA to identify the next steps” for the investigational injection, Martin Lange, executive vice president for development at Novo, said in a statement. “We believe in the potential of once-weekly basal insulin icodec for those living with diabetes who require basal insulin therapy,” Lange said.
The regulator’s rejection of icodec on Wednesday comes after the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee in May 2024 voted against its approval. In a 7-4 vote, the external advisors agreed that the current evidence show that icodec’s benefits do not outweigh its risks. The panelists pointed to the heightened risk of hypoglycemia versus the once-daily Tresiba (insulin degludec) in T1D patients.
The FDA’s internal reviewers flagged these same risks in their briefing document, released ahead of the advisory committee meeting. According to FDA staffers, while hypoglycemia is an expected side effect of insulin treatments, Novo’s once-weekly injection did not show “evidence of any additional glycemic control or other benefit” versus an active comparator.
The FDA briefing document also made the case that Novo did not sufficiently show that T1D patients preferred the once-weekly dosing schedule versus a daily injection.
Novo filed its application for icodec in April 2023, backing it with data from the ONWARDS clinical development program which included six Phase III studies. Five of these studies focused on type 2 diabetes, while only one included T1D patients.
According to the pharma’s briefing document for the adcomm meeting, icodec performed well in type 2 diabetes patients and was non-inferior to daily basal insulin in terms of HbA1c control with hypoglycemia being a relatively rare occurrence. In T1D, icodec was also non-inferior to daily injections, though the data revealed a “higher risk of clinically significant or severe hypoglycemic episodes.”
Novo has proposed including the hypoglycemia risk in icodec’s label, as well as limit the use of the weekly injection to patients with continuous glucose monitoring devices.
