▎WuXiEdited by Kant Content Team

Recently,The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending the granting of a marketing authorization for Awiqli (insulin icodec, a once-weekly basal insulin) for the treatment of diabetes in adults.Novo Nordisk expects to receive the final marketing authorization from the European Commission in approximately two months. In addition to the EU, Novo Nordisk also completed submissions of marketing applications to the U.S. FDA and Chinese regulatory authorities in the second quarter of 2023 and is currently awaiting the announcement of the review results.

This positive opinion from the CHMP is based on the results of the ONWARDS Phase 3a clinical trial program.Compared with daily injectable basal insulin, the once-weekly basal insulin icodec achieved greater reductions in blood glucose levels (measured by changes in HbA1c) and superior "time in range" (the amount of time within the recommended blood glucose range) in patients with type 2 diabetes.In patients with type 2 diabetes who had not previously received insulin therapy, the overall incidence rates of clinically significant hypoglycemia and severe hypoglycemia observed in both the Icodec insulin treatment group and the control group were less than 1 event per patient-year of exposure.

In patients with type 1 diabetes, insulin ecolin demonstrated non-inferiority to insulin degludec in lowering HbA1c, but showed a higher incidence of estimated severe hypoglycemia or clinically significant hypoglycemia, with a statistically significant difference.

Throughout the research project, Icodec insulin demonstrated safe and well-tolerated characteristics.

▲Icodec Six ItemsONWARDS Phase 3 Clinical Trial Results(Image source: Novo Nordisk official website)

Icodec insulin is a human insulin analog,Its amino acid structure has been altered in three places, with the addition of a C20 eicosanoic acid chain, enabling the molecule to reversibly bind to albumin, thereby extending its half-life to 196 hours (approximately 7 days), and after...3-4 timesA steady state is reached after weekly injections.The therapy is designed for once-weekly subcutaneous injection.

▲Icodec Insulin Structure (Image Source: Reference [5])

For the development of Insulin Icodec, Novo Nordisk launched the ONWARDS clinical research program, which includes six global Phase 3a clinical trials involving more than 4,000 adult patients with type 1 or type 2 diabetes to study the efficacy and safety of Insulin Icodec, with one trial incorporating real-world elements.In these Phase 3 trials, once-weekly insulin efsitora demonstrated non-inferiority and favorable safety in glycemic control compared to various types of once-daily insulin formulations.In some trials, insulin icodec demonstrated better blood glucose control.

▲Icodec InsulinONWARDS Clinical Development Program Overview(Image Source: Novo Nordisk's official website)

According to statistics from the World Health Organization (WHO), there are over 400 million diabetes patients globally. In response to diabetes, in addition to developing the long-acting insulin Icodec for once-weekly use, Novo Nordisk also has IcoSema in Phase 3 clinical trials for basal insulin research and development.IcoSema is a fixed-ratio combination of once-weekly basal insulin icodec and once-weekly semaglutide (700U/2 mg/mL).The results of the COMBINE 3 Phase 3a clinical trial, published in January this year, showed that among 679 patients with type 2 diabetes who had poor control with once-daily basal insulin,Once-weekly IcoSema demonstrated non-inferiority in lowering HbA1c compared to once-daily insulin therapy.In addition, Novo Nordisk also has several next-generation insulin products, including Tresiba, Xultophy, Ryzodeg, and Fiasp.

▲ Under Novo NordiskInsulin-related projects (Image source: Novo Nordisk's official website)

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References:

[1] European regulatory authorities recommend approval of Awiqli® (insulin efsitora, a once-weekly basal insulin) for the treatment of diabetes. Retrieved March 22, 2024 from https://www.novonordisk.com.cn/content/dam/nncorp/cn/zh_cn/ir-materials/pdfs/2024/2024032201.pdf

[2] Novo's weekly insulin secures CHMP thumbs-up as FDA decision looms. Retrieved March 22, 2024 from https://endpts.com/chmp-recommends-authorization-for-novo-nordisks-once-weekly-insulin-injection-awiqli/

[3] COMBINE 3 phase 3a trial successfully completed with once-weekly IcoSema demonstrating non-inferior reduction in HbA1c versus daily basal-bolus treatment (insulin glargine U100 and insulin aspart) in people with type 2 diabetes. Retrieved March 22, 2024 from https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167008#

[4] Bajaj HS, Goldenberg RM. Insulin Icodec Weekly: A Basal Insulin Analogue for Type 2 Diabetes. touchREV Endocrinol. 2023 May;19(1):4-6. doi: 10.17925/EE.2023.19.1.4. Epub 2023 Mar 16. PMID: 37313230; PMCID: PMC10258611.

[5] Kjeldsen TB, Hubálek F, Hjørringgaard CU, Tagmose TM, Nishimura E, Stidsen CE, Porsgaard T, Fledelius C, Refsgaard HHF, Gram-Nielsen S, Naver H, Pridal L, Hoeg-Jensen T, Jeppesen CB, Manfè V, Ludvigsen S, Lautrup-Larsen I, Madsen P. Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans. J Med Chem. 2021 Jul 8;64(13):8942-8950. doi: 10.1021/acs.jmedchem.1c00257. Epub 2021 May 4. PMID: 33944562.

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