By the end of the year, Novo Nordisk intends to make a regulatory filing for the combination of its icodec and semaglutide, keeping its once-weekly insulin program afloat.
Despite last month’s FDA rejection of its once-weekly insulin infusion, Novo Nordisk will push through with a filing for its investigational IcoSema this year, proposing the combination of insulin icodec with its blockbuster GLP-1 inhibitor semaglutide for the treatment of type 2 diabetes.
During last week’s second-quarter 2024 earnings results, Executive Vice President for Development Martin Holst Lange told analysts on a call that Novo is gearing up “to file for regulatory approval for IcoSema during the second half of 2024.”
The decision follows the completion of the pivotal Phase III COMBINE-1 study, Lange said, noting that the combo therapy “achieved its primary endpoint” by showing superior blood sugar control after 52 weeks versus insulin icodec alone. COMBINE-1 ran for 52 weeks and enrolled nearly 1,300 type 2 diabetes mellitus patients with inadequately controlled disease.
According to Novo’s Q2 presentation, IcoSema reduced baseline HbA1c levels by 1.6 percentage points, compared to only 0.9 percentage points for those patients who were treated with insulin icodec alone. The combo treatment also cut body weight by 3.7 kg, while control counterparts gained 1.9 kg after treatment with icodec alone.
The Danish pharma did not provide p-values but nevertheless claimed that IcoSema’s effects were statistically significant.
COMBINE-1 also found IcoSema to be safe and well-tolerated. Its rate of clinically significant or severe hypoglycemia was only 0.14 events per patient-years of exposure, significantly lower than the 0.63 frequency in patients treated with icodec alone.
Novo’s plans to file for IcoSema’s approval will help it keep its insulin icodec program afloat after the FDA last month rejected the once-weekly injection. The pharma had been seeking approval for insulin icodec in both type 1 and type 2 diabetes, though its data package leaned heavily toward the latter indication—five of the six late-stage studies in the application focused on type 2 diabetes.
This lack of evidence in type 1 diabetes ultimately cost Novo the approval, with the regulator citing concerns about icodec’s value in this indication in its Complete Response Letter. In a briefing document ahead of an advisory committee meeting, internal reviewers with the FDA flagged an excess risk of hypoglycemia in type 1 diabetes patients, which was not accompanied by “evidence of any additional glycemic control or other benefit.”
Combining semaglutide with insulin icodec might help Novartis reinvigorate its GLP-1 blockbuster amid a formidable challenge by fellow obesity frontrunner Eli Lilly. In Q2, sales of Lilly’s tirzepatide products Zepbound and Mounjaro beat analyst expectations, while Novo’s semaglutide line disappointed.
Lilly also appears to have the upper hand in terms of supply. Following months of shortages, all doses of Mounjaro and Zepbound are now available in the U.S., whereas one dose of Novo’s Wegovy remains in shortage—though the company continues to make strides in improving production.
