Novo Nordisk A/S: New data show once-weekly insulin icodec met additional endpoints in adults with type 2 diabetes in phase 3a trials

• After achieving primary endpoint by demonstrating superiority and non-inferiority in HbA_1C reduction from baseline at week 52, investigative insulin icodec helped patients achieve significantly more time in target blood glucose range (Time in Range) vs once-daily basal insulin glargine U100 in ONWARDS 1¹
• In the ONWARDS 1 and 3 trials, more people achieved blood glucose targets without clinically significant or severe hypoglycaemia with once-weekly basal insulin icodec vs once-daily basal insulin comparators^1,2
• Insulin icodec has been submitted for regulatory review in the US, Canada, Europe, China, Australia, Switzerland and Brazil. First decisions are anticipated in H1 2024

Bagsværd, Denmark, Sunday 25 June 2023 – Novo Nordisk today announced data from the phase 3a ONWARDS 1 and 3 trials evaluating investigative once-weekly basal insulin icodec, which were presented at the 83rd Annual Scientific Sessions of the American Diabetes Association (ADA). The data showed the studies met their primary endpoints, while reducing injections from seven to one per week, compared with once-daily basal insulin^1,2. Additionally, data from the ONWARDS 1 and 3 studies demonstrated that more insulin-naïve adults with type 2 diabetes treated with once-weekly basal insulin icodec achieved an HbA_1c target of <7.0% without experiencing clinically significant or severe hypoglycaemia compared with once-daily basal insulin comparators at 52 and 26 weeks, respectively^1,2.

In ONWARDS 1, as a confirmatory secondary endpoint, superior Time in Range (blood glucose 70–180 mg/dL) was achieved with once-weekly basal insulin icodec vs once-daily basal insulin glargine U100 (71.9% vs 66.9%, respectively) from week 48–52¹. Comparable Time below Range (blood glucose <54 mg/dL) was achieved with once-weekly basal insulin icodec vs once-daily basal insulin glargine U100 (0.3% vs 0.2%, respectively) from week 48–52 in ONWARDS 1¹. Both values are in line with internationally recommended targets³.

”Time in Range provides additional information to help us assess glycaemic control and is an increasingly important tool to complement HbA_1c measurements, which were substantially reduced by once-weekly basal insulin icodec. In ONWARDS 1, insulin icodec allowed people to spend significantly more Time in Range, with comparable Time below Range vs once-daily basal insulin glargine U100,” said Dr Julio Rosenstock, Lead Trial Investigator and Director of Velocity Clinical Research at Medical City Dallas and Clinical Professor of Medicine, University of Texas Southwestern Medical Center, US. “A once-weekly basal insulin has the potential to change how we treat people with type 2 diabetes needing basal insulin replacement.”

In ONWARDS 1, there were no statistically significant differences in mean weekly insulin dose (week 50–52) or in body weight change from baseline¹. Rates of clinically significant hypoglycaemia (blood glucose <54 mg/dL) or severe hypoglycaemia (symptomatic requiring third party assistance regardless of blood glucose measurement), were low in both treatment groups¹. Rates of clinically significant or severe hypoglycaemia were 0.30 events per patient year exposed and 0.16 events per patient year exposed to once-weekly insulin icodec and insulin glargine U100, respectively¹. A statistically significant higher proportion of participants achieved an HbA_1C target of <7% without clinically significant or severe hypoglycaemia with once-weekly basal insulin icodec vs once-daily basal insulin glargine U100 (52.6% vs 42.6%)¹.

In ONWARDS 3, rates of clinically significant or severe hypoglycaemia were 0.31 events per patient-year exposed and 0.15 events per patient-year exposed to insulin icodec and insulin degludec respectively, at weeks 0–31². The estimated proportion of participants achieving an HbA_1C target of <7% without clinically significant or severe hypoglycaemia was statistically significantly higher with once-weekly basal insulin icodec vs once-daily basal insulin degludec². There were no significant differences in mean weekly insulin dose from week 24 to 26 or body weight change from baseline to week 26 between treatment arms². No unexpected safety findings were observed^1,2.

“These data reinforce our confidence in the potential of once-weekly insulin icodec,” said Florian M.M. Baeres, corporate vice president, Global Medical Affairs at Novo Nordisk. “If approved, we believe this innovation – which would be the world’s first once-weekly basal insulin – could help people living with type 2 diabetes ready to start insulin treatment by reducing the number of injections needed.”

Insulin icodec has been submitted for regulatory review in the US, Canada, Europe, China, Australia, Switzerland and Brazil. First decisions are anticipated in H1 2024. Pending approval, insulin icodec will represent the first and only once-weekly basal insulin option for adults with diabetes, addressing an unmet need in treatment vs a daily basal insulin option^1,2,4–7.

For more news and media materials from Novo Nordisk at ADA 2023, please visit: https://www.novonordisk.com/news-and-media/ADA-e-press-room.

About insulin icodec
Insulin icodec is an investigational novel once-weekly basal insulin analog designed to cover the basal insulin requirements for a full week with a single subcutaneous injection.

About the ONWARDS clinical programme
The ONWARDS phase 3a trial programme for once-weekly basal insulin icodec comprises six phase 3a global clinical trials, including a trial with real-world elements, involving more than 4,000 adults with type 1 or type 2 diabetes⁸. All trials have met their primary endpoints^1,2,4–7.

About ONWARDS 1⁹
ONWARDS 1 is a phase 3a, 78-week, open-label efficacy and safety treat-to-target trial investigating once-weekly basal insulin icodec vs once-daily basal insulin glargine U100, both in combination with non-insulin anti-diabetic treatment, in 984 insulin-naïve adults with type 2 diabetes. The primary endpoint was change in HbA_1C from baseline at week 52 with insulin icodec compared with insulin glargine U100. Secondary endpoints included time in target blood glucose range (70–180 mg/dL), change in fasting plasma glucose (FPG) from baseline at week 52 and number of clinically significant or severe hypoglycaemia episodes. Following the completion of the 52-week main phase of the trial, a 26-week extension phase to further assess safety was undertaken and is now finalised.

About ONWARDS 3¹⁰
ONWARDS 3 is a phase 3a, double-blind 26-week efficacy and safety treat-to-target trial investigating once-weekly basal insulin icodec vs once-daily basal insulin degludec, both in combination with non-insulin anti-diabetic treatment. The objective of the trial was to assess the efficacy and safety of insulin icodec in 588 insulin-naïve adults with type 2 diabetes. The primary endpoint was change in HbA_1C from baseline at week 26. Secondary endpoints included change in fasting plasma glucose (FPG) from baseline at week 26 and number of clinically significant or severe hypoglycaemia episodes.

About Novo Nordisk
Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity and rare blood and endocrine disorders. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 57,100 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, Twitter, LinkedIn and YouTube.

Contact for further information

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References
1.      Rosenstock J, Bain SC, Gowda A, et al. Improved A1C and TIR with Once-Weekly Insulin Icodec vs Insulin Glargine U100 in Insulin-Naïve T2D: ONWARDS 1. 83rd Annual Scientific Sessions of the American Diabetes Association (ADA); 23–26 June 2023, San Diego; US. 179-OR.
2.      Lingvay I, Asong M, Desouza C, et al. Better Glycemic Control with Once-Weekly Insulin Icodec versus Once‑Daily Insulin Degludec in Insulin-Naïve Type 2 Diabetes (ONWARDS 3). 83rd Annual Scientific Sessions of the American Diabetes Association (ADA); 23–26 June 2023; San Diego, US. 178-OR.
3.      Battelino T, Danne T, Bergenstal RM, et al. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019;42(8):1593-1603.
4.      Philis-Tsimikas A, Asong M, Franek E, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11(6):414-425.
5.      Mathieu C, Asbjornsdottir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401(10392):1929-1940.
6.      Bajaj HS, Aberle J, Davies M et al. Superior Glycemic Control with Once-Weekly Insulin Icodec with a Dosing Guide App vs Once-Daily (OD) Basal Insulin Analogs in Insulin-Naïve T2D: ONWARDS 5. American Diabetes Association (ADA) – 83rd Scientific Sessions, 23-26 June 2023, San Diego, US. 803-P.
7.      Novo Nordisk. Company announcement. Novo Nordisk achieves primary objectives of ONWARDS 1 and 6 trials with once-weekly insulin icodec demonstrating superior reduction in HbA1c vs insulin glargine U100 in ONWARDS 1. Available at: https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=118349 Last accessed: June 2023.
8.      Philis-Tsimikas A, Bajaj HS, Begtrup K, et al. Rationale and design of the phase 3 development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2022.
9.      ClinicalTrials.gov. A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 1). Available at: https://clinicaltrials.gov/ct2/show/NCT04460885 Last accessed: June 2023.
10.      ClinicalTrials.gov. A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3). Available at: https://clinicaltrials.gov/ct2/show/NCT04795531 Last accessed: June 2023.

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• PR230624-ADA-Icodec-ONWARDS