FDA Flags Hypoglycemia Risk for Novo’s Once-Weekly Insulin Ahead of Adcomm

Novo Nordisk_iStock, hapabapa

Pictured: Facade of Novo Nordisk's office in Fremont, California/iStock, hapabapa

With an advisory committee meeting slated for Friday, the FDA has identified “excess hypoglycemia” associated with Novo Nordisk’s insulin icodec, which the pharma is proposing as a once-weekly injection for diabetes mellitus.

In its briefing document, the regulator’s reviewers flagged what they called a “significantly higher” rate of hypoglycemic episodes in type 1 diabetes (T1D) patients treated with insulin icodec, compared with insulin degludec.

While hypoglycemia is an “expected adverse reaction” in patients who inject insulin, Novo’s once-weekly injection did not show “evidence of any additional glycemic control or other benefit” in T1D patients versus the active comparator, the FDA’s staffers wrote.

“The patient-focused data … were inadequate to inform whether patients with T1D preferred the once-weekly basal insulin option to once-daily,” the FDA reviewers concluded.

Novo is proposing insulin icodec to help glycemic control in patients with diabetes, but the panel of external experts will focus its discussions on the “benefits and risks of insulin icodec in patients with T1D.”

Insulin icodec is a long-acting analog of insulin that hopes to differentiate itself from other once-daily insulin products on the market by offering a once-weekly dosing option. According to Novo’s briefing document for the adcomm meeting, insulin icodec contains a fatty acid side chain that allows it to bind to circulating albumin which in produces “a depot of essentially inactive insulin icodec,” from which the drug can be “slowly and continuously released.”

To determine the effect of once-weekly insulin icodec on glycemic control, the Danish drugmaker ran the ONWARDS clinical development program, which consisted of six Phase III studies. Only one of these studies—ONWARDS 6—included patients with T1D.

The trial demonstrated that Novo’s once-weekly injection was non-inferior to daily basal insulin in terms of glycemic improvement, but also found that treated patients had a higher risk of “clinically significant” or “severe” hypoglycemic episodes.

Still, Novo maintains that the hypoglycemia risks “can be effectively managed by guidance” from physicians and that “the availability of a weekly insulin could provide an important and unique alternative treatment option for some people living with T1D.”

According to the FDA’s briefing document, Novo has proposed to flag this hypoglycemia risk in insulin icodec’s label, guiding prescribers to limit its use to patients with continuous glucose monitoring devices and to those with low glycemic variability. The label will also recommend the discontinuation of insulin icodec in case of recurring hypoglycemia.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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