Novo Nordisk has resubmitted its biologics license application (BLA) to the FDA for Awiqli (insulin icodec) injection, a once-weekly basal insulin treatment for adults living with type 2 diabetes. If approved, this would mark the first once-weekly basal insulin available in the United States, offering a significant advancement in diabetes management for the approximately 34 million Americans with type 2 diabetes.
Clinical Development Program
The resubmission is based on results from the ONWARDS type 2 diabetes phase 3a program, which comprises five randomized, active-controlled, treat-to-target clinical trials involving approximately 4,000 adults with type 2 diabetes. The clinical program evaluated weekly Awiqli versus daily basal insulin, with the primary endpoint being change in A1C from baseline.
"With this resubmission, we're closer to offering a new insulin treatment option for people living with type 2 diabetes that, if approved, could reduce their yearly basal insulin injections from 365 to 52," said Anna Windle, Ph.D., senior vice president, clinical development, medical and regulatory affairs at Novo Nordisk.
Mechanism of Action
Awiqli is a long-acting insulin analog with a prolonged half-life of approximately seven days. The drug binds to albumin, a protein in the blood, to form an inactive depot that is released throughout the week. This mechanism allows for once-weekly subcutaneous injection rather than daily administration.
Regulatory Journey
The resubmission follows the FDA's complete response letter from July 2024, which raised concerns about the manufacturing process and the type 1 diabetes indication. Novo Nordisk had originally submitted the application for Awiqli in April 2023 for use in patients with either type 1 or type 2 diabetes.
In May 2024, an FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting convened a panel of independent scientific experts to discuss the benefit-risk profile of once-weekly basal insulin icodec in type 1 diabetes. The panel voted 7-4, determining that the available data were insufficient to conclude that the benefits of insulin icodec outweigh its risks in type 1 diabetes patients. Notably, the advisory committee did not discuss the use of once-weekly insulin icodec in patients with type 2 diabetes.
Type 1 Diabetes Concerns
A previous phase 3 study, ONWARDS 6, evaluated insulin icodec in 4,625 patients with type 1 diabetes, with results published in The Lancet in October 2023. The study compared insulin icodec with once-daily degludec (Tresiba) in a non-inferiority study. While once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, regulators were concerned about the significantly higher rate of hypoglycemic episodes in the insulin icodec arm compared with the insulin degludec arm.
Strategic Focus
A Novo Nordisk spokesperson indicated that the company prioritized the resubmission in adults with type 2 diabetes to avoid delays. The company plans a new trial for patients with type 1 diabetes and remains "committed to people living with type 1 diabetes and see important potential for Awiqli in this community."
Global Approval Status
Awiqli is currently approved in 13 countries, including the European Union, providing precedent for its safety and efficacy profile in international markets.
