Juan Frias, MD
Credit: Novo Nordisk

A release of data from the ONWARDS program at the 83rd scientific sessions of the American Diabetes Association (ADA 2023) provide the latest evidence in support of once-weekly insulin icodec.

Presentations of data from the phase 3a ONWARDS 1 and ONWARDS 3, results added further insight into the efficacy of once-weekly insulin icodec relative to other forms of insulin, and in both type 1 and type 2 diabetes, as the agent appears to be headed toward a potential regulatory decision following the submission of a biologics license application by Novo Nordisk in April 2023.¹

"These data reinforce our confidence in the potential of once-weekly insulin icodec," said Florian M.M. Baeres, corporate vice president of 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."

ONWARDS Program Overview

ONWARDS 1

A 78-week efficacy and safety treat-to-target trial, ONWARDS 1 compared once-weekly insulin icodec against once-daily insulin glargine U100 in insulin-naive adults with type 2 diabetes with inadequate glycemic control. The trial enrolled 984 patients using non-insulin antidiabetes treatments and had a primary endpoint of change from baseline to week 52 in HbA1c with insulin icodec relative to insulin glargine U100. Results of the trial detailed a mean HbA1c reduction of -1.55% with once-weekly insulin icodec compared to -1.35% with insulin glargine U100 (estimated treatment difference [ETD], -0.19%).²

ONWARDS 2

A 26-week efficacy and safety treat-to-target trial, ONWARDS 2 compared once-weekly insulin icodec against once-daily insulin degludec in adults with type 2 diabetes switching from daily insulin. The trial enrolled 526 patients and had a primary endpoint of change from baseline to week 26 in HbA1c with insulin icodec relative to insulin degludec. Results of the trial suggested use of insulin icodec was associated with a superior reduction in HbA1c of -0.93% compared to -0.71% with insulin degludec (ETD, -0.22%).³

ONWARDS 3

A 26-week efficacy and safety treat-to-target trial, ONWARDS 3 compared once-weekly insulin icodec against once-daily insulin degludec in combination with non-insulin anti diabetes treatment in insulin-naive adults with type 2 diabetes. The trial enrolled 588 patients and had a primary endpoint of demonstrating noninferiority for reducing HbA1c at week 26 with insulin icodec relative to insulin degludec. Results of the trial detailed a mean reduction in HbA1c of -1.57% for the insulin icodec group compared to -1.36% for the insulin degludec group (ETD, -0.21%).⁴

ONWARDS 4

A 26-week efficacy and safety treat-to-target trial, ONWARDS 4 compared use of once-weekly insulin icodec against once-daily insulin glargine U100, both in combination with mealtime insulin, in adults with type 2 diabetes. The trial enrolled 582 patients and had a primary endpoint of demonstrating noninferiority for reducing HbA1c at week 26 with insulin icodec relative to insulin glargine U100. Results of the trial suggested use of insulin icodec was associated with a mean reduction in HbA1c of -1.16% compared to -1.18% for insulin glargine U100 (ETD, 0.02%).⁴

ONWARDS 5

A 52-week efficacy and safety treat-to-target trial, ONWARDS 5 compared use of once-weekly insulin icodec against once-daily basal insulin, either insulin degludec or insulin glargine U100/U300, in insulin-naive adults with type 2 diabetes. Of note, ONWARDS 5 contained fewer trial visits than other ONWARDS trials and patients used once-weekly insulin icodec in combination with a dosing guide app for optimal uptitration. The trial enrolled 1085 patients and had a primary endpoint of demonstrating noninferiority for reducing HbA1c at week 26 with insulin icodec relative to basal insulins. Results of the trial detailed a mean reduction in HbA1c of -1.68% for the insulin icodec group compared to -1.31% for the once-daily basal insulins group (ETD, -0.38%).⁵

ONWARDS 6


A 52-week efficacy and safety treat-to-target trial, ONWARDS 6 compared use of once-weekly insulin icodec against once-daily insulin degludec, both in combination with 3 daily mealtime insulin injections, in adults with type 1 diabetes. The trial enrolled 582 patients and had a primary endpoint of demonstrating noninferiority for reducing HbA1c at week 26 with insulin icodec relative to insulin degludec. Results of the trial suggested once-weekly insulin icodec was associated with a mean HbA1c reduction of -0.47% compared to -0.51% for insulin degludec (ETD, 0.05%).²

For more insight into the prospect of once-weekly insulin icodec as a potential regulatory decision looms in the future, our editorial team sat down with ONWARDS program investigator Juan Frias, MD, medical director and principal investigator of Velocity Clinical Research, at ADA 2023.

Relevant disclosures for Dr. Frias include Akero Therapeutics, Inc, 89bio, Inc, Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Novartis, Pfizer Inc., Sanofi, and others.

References:

1. New data show once-weekly insulin icodec met additional endpoints in adults with type 2 diabetes in phase 3a trials. Novo Nordisk. June 24, 2023. Accessed June 30, 2023. https://www.novonordisk-us.com/content/nncorp/us/en_us/media/news-archive/news-details.html?id=166123.
2. 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. Novo Nordisk. June 3, 2022. Accessed June 30, 2023. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=118349.
3. Once-weekly insulin icodec demonstrates superior reduction in HbA1c vs insulin degludec in people with type 2 diabetes in ONWARDS 2 phase 3a trial. Novo Nordisk. April 28, 2022. Accessed June 30, 2023. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=112839#.
4. Novo Nordisk achieves primary objectives of ONWARDS 3 and 4 trials with once-weekly insulin icodec demonstrating superior reduction in HbA1c vs insulin degludec in ONWARDS 3. Novo Nordisk. July 29, 2022. Accessed June 30, 2023. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=127304.
5. Once-weekly insulin icodec demonstrates superior reduction in HbA1c in combination with a dosing guide app versus once-daily basal insulin in people with type 2 diabetes in ONWARDS 5 phase 3a trial. Novo Nordisk. October 3, 2022. Accessed June 30, 2023. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=138024.