As Novo Nordisk moves full speed ahead on global regulatory filings for a combination of once-weekly insulin icodec and semaglutide, the U.S. won’t be part of that plan, for now, thanks to a recent regulatory hiccup with the FDA.
Following a positive readout in the late-stage COMBINE 1 trial, Novo is planning to submit applications for IcoSema during the second half of 2024, Martin Holst Lange, M.D., Ph.D., executive vice president of development at Novo Nordisk, said on a recent analyst call.
Still, the company won’t be able to file in the U.S. given that icodec, the insulin component of the combination Type 2 diabetes candidate, was recently slapped with a complete response letter by the FDA, a company spokesperson told Fierce.
IcoSema is a combination of once-weekly insulin icodec and once-weekly semaglutide for the treatment of Type 2 diabetes. Semaglutide is the molecule underpinning Novo’s immensely popular GLP-1 drugs Ozempic and Wegovy.
Icodec has been approved as Awiqli in places like Europe, Canada, Japan and Australia but was snubbed by the FDA last month.
In its rejection, the U.S. agency made “requests related to the manufacturing process and the type 1 diabetes indication,” Novo said at the time. The company said it didn’t expect to remedy the issues before 2024 is out.
The rejection came about seven weeks after an FDA panel of outside experts recommended against approving the once-a-week insulin product, raising questions about icodec’s risk of causing low blood sugar.
As for the data the company will leverage to seek approval for IcoSema elsewhere, Novo’s COMBINE 1 study sought to assess the safety and efficacy of switching to once-weekly IcoSema from once-weekly insulin icodec in Type 2 diabetes patients whose disease was inadequately controlled on daily basal insulin with or without oral diabetes drugs.
Ultimately, IcoSema proved superior at reducing A1c—a measure of a patient’s blood sugar over time—compared to insulin icodec at the trial’s 52-week mark, meeting the study’s primary objective, Lange told investors last week.
From an overall HbA1c base line of 8.2%, IcoSema helped patients reduce their A1c by 1.6% versus 0.9% with insulin icodec, the executive explained.
Treatment with IcoSema also helped patients lose around 3.7 kg (8.2 pounds) versus a 1.9-kg (4.2-pound) weight gain for patients on insulin icodec.
Further, patients on IcoSema experienced a “typically significantly lower” rate of major hypoglycemia events (0.14 events per patient years of exposure) versus insulin icodec (0.63 events per patient year of exposure), according to Lange.
The executive added that IcoSema appeared to be safe and well tolerated.
Meanwhile, Novo’s chief rival in diabetes and weight loss, Eli Lilly, is testing its own once-weekly insulin.
In May, Lilly unveiled data from a pair of phase 3 studies showing its candidate, efsitora alfa, was noninferior to daily insulin at 52 weeks, with patients’ A1c falling 1.34% and 1.26%, respectively.
Editor's note: This story replaces a previous version that incorrectly stated Novo Nordisk would be filing for approval of IcoSema in the U.S. this year.