Novo Nordisk to file for regulatory approval of once-weekly insulin icodec next year

The Danish pharma group said it expects to file for regulatory approval of once-weekly insulin icodec in the US, the EU and China in the first half of 2023.

Novo Nordisk has announced headline results from the ONWARDS 5 phase 3a trial with once-weekly insulin icodec in people with type 2 diabetes, a 52-week study comparing once-weekly insulin icodec with once-daily basal insulin.

The objective of the study was to assess the effectiveness and safety of insulin icodec, with an app providing dosing recommendation, in 1,085 insulin-naïve people with type 2 diabetes in a clinical practice setting.

The trial included no upper limit in terms of hemoglobin A1c (HbA1c) levels at time of inclusion, no limitations on use of oral antidiabetic treatments and fewer planned site visits compared to the other ONWARDS phase 3a trials.

Results

The study achieved its primary endpoint, said the developer. It demonstrated non-inferiority in reducing HbA1c at week 52 with insulin icodec compared with once-daily basal insulin analogues.

“From an overall baseline HbA1c of 8.9%, once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of –1.68%-points compared with –1.31%-points for the once-daily basal insulins.”​

In the trial, there was no statistically significant difference in estimated rates of severe or clinically significant hypoglycaemia (blood glucose below 3 mmol/L) with 0.19 events per patient-year exposed to once-weekly insulin icodec and 0.14 events per patient-year exposed to the once-daily basal insulins. And the once-weekly insulin icodec appeared to have a safe and well-tolerated profile in the participants, said the Danish company.

“These results include real-world elements and a dosing guide app, which help us better understand how insulin icodec can make a difference for patients in a clinical practice setting,”​ said Martin Holst Lange, executive vice president for development, Novo Nordisk.

The results confirm the findings of previously reported ONWARDS trials and highlight that insulin icodec has the potential to be an ideal insulin for people with type 2 diabetes, he added. “We now look forward to sharing the results with regulatory authorities.”​

Weekly insulin injections: a new treatment paradigm?​

Novo Nordisk has long been a pioneer in terms of innovation in the diabetes treatment space, Mads Frederik Rasmussen, senior vice president of clinical drug development at that pharma giant, told this publication in February.

And he explained then why the company’s once-weekly Insulin icodec injection represented a new treatment paradigm for diabetes:

“Insulin first started being produced for the treatment of diabetes 100 years ago. Since then, there have been many large and small steps forward in innovation, such as the first purified insulin, going from animal-based to human insulin, the invention of insulin analogues with faster or longer action and the development of increasingly convenient delivery solutions. Each of these steps have helped ensure that people with diabetes have been able to live longer and have a better quality of life, but we also know that not all people with diabetes are in good glycemic control. We believe that our investigational weekly insulin icodec has the potential to offer a new standard of care in this space.”​

ONWARDS program​

The ONWARDS 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.

Besides the ONWARDS 5 trial, the program includes the following studies:

• ONWARDS 1 is a 78-week trial comparing the efficacy and safety of once-weekly insulin icodec with once-daily insulin glargine U100 both in combination with non-insulin anti-diabetic treatment in 984 insulin-naïve people with type 2 diabetes. Following the completion of the main phase of the trial, a 26-week extension phase is ongoing. The results of the main phase were reported on 3 June 2022.
• ONWARDS 2 was a phase 3a, 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec in 526 people with type 2 diabetes switching from a once-daily insulin. Results were reported on 28 April 2022.
• ONWARDS 3 was a 26-week trial comparing once-weekly insulin icodec with once-daily insulin degludec. The objective of the trial was to assess the efficacy and safety of insulin icodec in 588 insulin-naïve people with type 2 diabetes. Results were reported on 29 July 2022.
• ONWARDS 4 was a 26-week trial comparing once-weekly insulin icodec with once-daily insulin glargine, both in combination with mealtime insulin. The objective of the trial was to assess the efficacy and safety of insulin icodec in 582 people with type 2 diabetes treated with basal and bolus insulin. Results were reported on 29 July 2022.
• ONWARDS 6 is a 52-week trial comparing once-weekly insulin icodec with once-daily insulin degludec, both in combination with mealtime insulin. The objective of the trial is to assess the efficacy and safety of insulin icodec in 583 people with type 1 diabetes. Following the completion of the main phase of the trial, a 26-week extension phase is ongoing. The results of the main phase were reported on 3 June 2022.