FDA Issues Complete Response Letter for Once-Weekly Insulin Icodec

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to once-weekly basal insulin icodec for the treatment of diabetes mellitus.¹

Announced on July 10, 2024, by Novo Nordisk, the CRL included requests concerning the manufacturing process and the type 1 diabetes (T1D) indication, which must be addressed before the Biologics License Application (BLA) review for insulin icodec can be completed.

In their release, Novo Nordisk indicated its intention to review the requests in the CRL and work closely with the FDA to determine the next steps. However, the company does not anticipate fulfilling these requests this year.

“We believe in the potential of once-weekly basal insulin icodec for those living with diabetes who require basal insulin therapy,” said Martin Lange, executive vice president for development at Novo Nordisk. “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.”

In May 2024, an FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting hosted a panel of independent scientific experts to evaluate the benefit-risk profile of once-weekly basal insulin icodec in T1D.²

Concluding with a 7–4 vote, the committee determined the available data were insufficient to conclude the benefits of insulin icodec outweigh its risk profile. The Advisory Committee meeting did not discuss the use of once-weekly insulin icodec in type 2 diabetes (T2D).

Novo filed its initial application for insulin icodec to the regulatory agency in April 2023, based on data from the ONWARDS clinical program of six Phase 3 studies.³ The ONWARDS 1–5 trials focused on patients with T2D, while ONWARDS 6 evaluated patients with T1D.

ONWARDS 1 evaluated once-weekly insulin icodec against once-daily insulin glargine U100 in insulin-naive adults with T2D and inadequate glycemic control. Results favored insulin icodec, with a –1.55% reduction in mean HbA1c at Week 52 relative to –1.35% with insulin glargine U100.

ONWARDS 2 compared once-weekly insulin icodec against once-daily insulin degludec in adults with T2D switching from daily insulin. Insulin icodec was associated with a superior reduction in HbA1c of –0.93% compared to –0.71% with insulin degludec at Week 26.

ONWARDS 3 assessed once-weekly insulin icodec against once-daily insulin degludec in combination with non-insulin anti-diabetes treatment in insulin-naive adults with T2D. A mean reduction in HbA1c of –1.57% was achieved in the insulin icodec group, compared to –1.36% in the insulin degludec group, at Week 26.

ONWARDS 4 compared the use of once-weekly insulin icodec versus once-daily insulin glargine U100, in combination with mealtime insulin, in adults with T2D. Insulin icodec was associated with a mean reduction in HbA1c of –1.16%, compared to –1.18% for insulin glargine U100, at Week 26.

ONWARDS 5 evaluated the use of once-weekly insulin icodec against once-daily basal insulin, either insulin degludec or insulin glargine U100/U300, in insulin-naive adults with T2D. Results favored insulin icodec with a mean HbA1c reduction of –1.68% compared with –1.31% for once-daily basal insulin at Week 26.

ONWARDS 6 assessed the use of once-weekly insulin icodec against once-daily insulin degludec, in combination with 3 daily mealtime insulin injections, in adults with T1D. Once-weekly insulin icodec was associated with a mean HbA1c reduction of –0.47%, compared to –0.51% for insulin degludec, at Week 26.

Insulin icodec is currently approved under the brand name Awiqli® in the European Union, Canada, Australia, Japan and Switzerland for the treatment of T1D and T2D, and in China for the treatment of T2D.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. _{Manalac T. Novo Nordisk’s once-weekly insulin loses FDA Adcomm vote for type 1 diabetes. BioSpace. May 28, 2024. Accessed July 11, 2024. https://www.biospace.com/article/novo-nordisk-s-once-weekly-insulin-loses-fda-adcomm-vote-for-type-1-diabetes/.}
3. _{Campbell P. The prospect of once-weekly basal insulin, with Juan Frias, MD. HCP Live. June 30, 2023. Accessed July 11, 2024. https://www.hcplive.com/view/the-prospect-of-once-weekly-basal-insulin-with-juan-frias-md.}