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 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 hypoglycemia with once-weekly insulin icodec vs. once-daily basal insulin comparators^1-2
• Novo Nordisk submitted a biologics license application to the US FDA for insulin icodec, the first investigational once-weekly insulin, based on data from the ONWARDS program

SAN DIEGO, June 24, 2023 /PRNewswire/ -- Novo Nordisk today announced that data from the phase 3a ONWARDS 1 and 3 trials evaluating investigative once-weekly insulin icodec, which were presented at the 83^rd Annual Scientific Sessions of the American Diabetes Association (ADA), showed the studies met their primary endpoints and insulin icodec provided similar glucose-lowering effects (change in HbA_1C from baseline) 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 insulin icodec achieved an HbA_1c target of <7.0% without experiencing clinically significant or severe hypoglycemia 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 insulin icodec vs. once-daily basal insulin glargine U100 (71.9% vs. 66.9%, respectively; p=0.0004) from week 48-52¹. Comparable Time below Range (blood glucose <54 mg/dL) was achieved with once-weekly 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 glycemic 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. "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 baseline. Level 2 (blood glucose <54 mg/dL) or 3 (symptomatic hypoglycemia requiring third party assistance regardless of blood glucose measurement) hypoglycemia rates (baseline to week 52) were low in both treatment groups, with numerically higher rates with insulin icodec. Rates of clinically significant (level 2) or severe (level 3) hypoglycemia were 0.30 events per patient year exposed and 0.16 events per patient year exposed to once-weekly insulin icodec and once-daily insulin glargine U100, respectively. A higher proportion of participants achieved an HbA_1C target of <7% without level 2 or 3 hypoglycemia with insulin icodec vs. insulin glargine U100 (52.6% vs. 42.6%, p=0.0028). In ONWARDS 3, level 2 or 3 hypoglycemia rates were numerically higher with once-weekly insulin icodec vs. once-daily insulin degludec. Rates of clinically significant (level 2) or severe (level 3) hypoglycemia were 0.31 events per patient year exposed and 0.15 events per patient year exposed to insulin icodec and insulin degludec, respectively. The estimated proportion of participants achieving an HbA_1C target of <7% without level 2 or 3 hypoglycemia was statistically significantly higher with insulin icodec vs. insulin degludec. 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 arms. 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 per week."

Based on data from the ONWARDS clinical trial program, Novo Nordisk submitted a biologics license application (BLA) in April 2023 to the US Food & Drug Administration (FDA) for once-weekly insulin icodec for the treatment of diabetes. A decision from the agency is anticipated in April of 2024. If approved, 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^4-9.

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 program
The ONWARDS phase 3a trial program for once-weekly 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 diabetes^4-9. All trials have met their primary endpoints.

About ONWARDS 1⁷
ONWARDS 1 is a phase 3a, 78-week, open-label efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs. once-daily 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 to week 52 with insulin icodec compared to insulin glargine U100. Secondary endpoints included time in target blood glucose range (70-180 mg/dL), change in fasting plasma glucose (FPG) from baseline to week 52 and number of clinically significant (level 2) or severe (level 3) hypoglycemia 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 finalized.

About ONWARDS 3⁶
ONWARDS 3 is a phase 3a, double-blind 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs. 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 to week 26. Secondary endpoints included change in fasting plasma glucose (FPG) from baseline to week 26 and number of clinically significant (level 2) or severe (level 3) hypoglycemia episodes.

About Novo Nordisk
Novo Nordisk is a leading global healthcare company that has been making innovative medicines to help people with diabetes lead longer, healthier lives for 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity and rare blood and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and production and research facilities in seven states, Novo Nordisk employs nearly 6,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, and Twitter.

Contact for further information

Further information
Media:   
Nicole Ferreira (US)
+1 609 786 5868
[email protected]

Investors:     
Mark Joseph Root (US)
+1 848 213 3219
[email protected]   

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;42:1593-1603.
4. ClinicalTrials.gov. A Research Study to Compare a New Weekly Insulin, Insulin Icodec, and an Available Daily Insulin, Insulin Degludec, Both in Combination With Mealtime Insulin in People With Type 1 Diabetes (ONWARDS 6). Available at: https://clinicaltrials.gov/ct2/show/NCT04848480 Last accessed: June 2023.
5. ClinicalTrials.gov. A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4). Available at: https://clinicaltrials.gov/ct2/show/NCT04880850 Last accessed: June 2023.
6. 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.
7. 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.
8. ClinicalTrials.gov. A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin (ONWARDS 2). Available at: https://clinicaltrials.gov/ct2/show/NCT04770532 Last accessed: June 2023.
9. ClinicalTrials.gov. A Research Study to Compare a New Weekly Insulin, Insulin Icodec Used With DoseGuide App, and Daily Insulins in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 5). Available at: https://clinicaltrials.gov/ct2/show/NCT04760626 Last accessed: June 2023.

Novo Nordisk is a registered trademark of Novo Nordisk A/S.

© 2023 Novo Nordisk All rights reserved. US23DI00142 June 2023

SOURCE Novo Nordisk