FDA Issues Complete Response Letter to Novo Nordisk for Icodec, a Once-Weekly Basal Insulin for the Treatment of Diabetes Mellitus

The FDA has issued a Complete Response Letter (CRL) to Novo Nordisk regarding its Biologics License Application (BLA) for once-weekly basal insulin icodec, a treatment for diabetes mellitus. According to the CRL, the FDA has requested additional information related to the treatment’s manufacturing process and the indication for type 1 diabetes before it can complete its review.¹

“We believe in the potential of once-weekly basal insulin icodec for those living with diabetes who require basal insulin therapy,” said Martin Lange, EVP, development, Novo Nordisk, in a press release. “We will work closely with the FDA to identify the next steps needed to complete the review so we can provide this novel treatment option to adults living with diabetes.”

Novo Nordisk initially submitted the BLA to the FDA for insulin icodec in April 2023. This past May, an FDA Advisory Committee evaluated its benefit-risk profile in patients with type 1 diabetes but found the data insufficient for a positive conclusion; however, the committee did not review the use of insulin icodec for type 2 diabetes.

Currently, the treatment is approved under the name Awiqli in a number of countries including the EU, Canada, Australia, Japan and Switzerland for the treatment of both type 1 and type 2 diabetes and in China for the treatment of type 2 diabetes.1 These approvals were based on results from the ONWARDS clinical development program, which consisted of six Phase IIIa clinical trials investigating the efficacy and safety of once-weekly insulin icodec. Enrolling over 4,000 patients with type 1 or type 2 diabetes, the trials included real-world elements.²

Results of the six trials found as follows:

• ONWARDS 1: At week 52, insulin icodec demonstrated non-inferiority and superiority versus insulin glargine U100 in reducing the estimated mean HbA1c from baseline.
• ONWARDS 2: At week 26, insulin icodec demonstrated non-inferiority and superiority versus insulin degludec in reducing the estimated mean HbA1c from baseline.
• ONWARDS 3: At week 26, insulin icodec demonstrated non-inferiority and superiority versus insulin degludec in reducing the estimated mean HbA1c from baseline.
• ONWARDS 4: At week 26, insulin icodec demonstrated non-inferiority versus insulin glargine U100 in reducing the estimated mean HbA1c from baseline.
• ONWARDS 5: At week 52, insulin icodec used in conjunction with dosing guide app demonstrated non-inferiority and superiority versus basal insulin analogues in reducing the estimated mean HbA1c from baseline.
• ONWARDS 6: At week 26, insulin icodec demonstrated non-inferiority versus insulin degludec in reducing the estimated mean HbA1c from baseline.²

In June 2023, Novo Nordisk presented data from the ONWARDS 1 and ONWARDS 3 trials at the 83rd Annual Scientific Sessions of the American Diabetes Association.³

“Time in Range provides additional information to help us assess glycaemic control and is an increasingly important tool to complement HbA1c 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 Julio Rosenstock, MD, lead trial investigator, director, Velocity Clinical Research, Medical City Dallas, clinical professor of Medicine, University of Texas Southwestern Medical Center, US, in a press release “A once-weekly basal insulin has the potential to change how we treat people with type 2 diabetes needing basal insulin replacement.”

While Novo Nordisk is currently reviewing the requests made in the CRL, the company stated that they do not expect to complete the process by the end of the year.¹

References

1. Novo Nordisk receives Complete Response Letter in the US for once-weekly basal insulin icodec. Novo Nordisk. July 10, 2024. Accessed July 11, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=168532

2. Overview of the main phase of the ONWARDS phase 3 clinical development programme for investigational once-weekly insulin icodec. Novo Nordisk. Accessed July 11, 2024. file:///Users/donaldtracy/Downloads/Novo%20Nordisk%20ONWARDS%20phase%203%20trials%20infographic_FINAL_20.06.23.pdf

3. 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 July 11, 2024. https://www.novonordisk.com/content/dam/nncorp/global/en/media/images/e-press-room/ada-e-press/assets/insulin/Novo%20Nordisk%20press%20release%20insulin%20icodec%20phase%203%20data%20at%20ADA_June%202023.pdf