[Translation] A 40-week study comparing the efficacy and safety of once-weekly IcoSema with once-daily insulin glargine 100 units/ml in subjects with type 2 diabetes who were inadequately controlled on oral glucose-lowering medications. COMBINE 4

本研究将在接受其他口服降糖药物治疗但血糖控制不佳的2型糖尿病患者中考察IcoSema相比于甘精胰岛素在控制血糖水平方面的疗效。

[Translation]

This study will investigate the efficacy of IcoSema compared with insulin glargine in controlling blood sugar levels in patients with type 2 diabetes who have poor blood sugar control despite other oral glucose-lowering medications.

Start Date07 Mar 2024

Sponsor / Collaborator

Novo Nordisk China Pharmaceuticals Co. Ltd.

[+1]

NCT06269107

/ Active, not recruitingPhase 3

A 40-week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL in Participants With Type 2 Diabetes Inadequately Controlled on Oral Anti Diabetic Drugs COMBINE 4

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine (mentioned as insulin glargine in this form) taken daily in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar levels as compared to insulin glargine in people with type 2 diabetes who do not have their blood sugar properly controlled with other oral diabetes medicines. Participant will either get IcoSema or insulin glargine. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine in many countries. The study will last for about 11 months (47 weeks).

Start Date15 Feb 2024

Sponsor / Collaborator

Novo Nordisk A/S

JPRN-jRCT2031230600

/ SuspendedPhase 3IIT

A 40-week study comparing the efficacy and safety of once weekly IcoSema and daily insulin glargine 100 units/mL in participants with type 2 diabetes inadequately controlled on oral anti-diabetic drugs. (NN1535-4988:COMBINE 4) - COMBINE 4

Start Date15 Feb 2024

Sponsor / Collaborator-

100 Clinical Results associated with Icodec Insulin/Semaglutide

100 Translational Medicine associated with Icodec Insulin/Semaglutide

100 Patents (Medical) associated with Icodec Insulin/Semaglutide

Literatures (Medical) associated with Icodec Insulin/Semaglutide

02 Jan 2025·Expert Opinion on Pharmacotherapy

Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II

Review

Author: Davis, Stephen N. ; Siamashvili, Maka

INTRODUCTIONA stepwise coordinated multiple therapeutic targeted approach to the treatment of type 2 diabetes includes starting with lifestyle modification, oral antihyperglycemic agents, non-insulin injectables (Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and both short and long-acting insulins. Ultra-long-acting insulins offer more convenient administration. As in any chronic disease, the introduction of a novel medication must balance safety, efficacy, financial cost, as well as improved patient convenience and adherence.AREAS COVEREDThis manuscript describes IcoSema - a new investigational fixed-ratio combination of basal insulin icodec and the GLP-1 RA semaglutide. The key trials from the clinical development process of insulin icodec, semaglutide, and IcoSema are reviewed with important endpoints highlighted.EXPERT OPINIONOnce-weekly IcoSema offers glycemic efficacy that is non-inferior to glargine+aspart, similar risk of hypoglycemia, significant reduction in body weight, the convenience of use, and favorable safety profile with most adverse events being gastrointestinal.

27 Nov 2024·Journal of Basic and Clinical Physiology and Pharmacology

IcoSema’s leap forward: new data from COMBINE 3 paves the way

Author: Seetharaman, Rajmohan

01 Nov 2024·Clinical Drug Investigation

Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus

Article

Author: Rocha, Thaís M P ; Nishimura, Erica ; Kristensen, Niels R ; Nørgreen, Lea ; Klitgaard, Thomas ; Steensgaard, Dorte B ; Westergaard, Lisbet ; Plum-Mörschel, Leona ; Buckley, Stephen T ; Alifrangis, Lene ; Vegge, Andreas ; Coester, Hans Veit

BACKGROUND AND OBJECTIVEIcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM).METHODSIn a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose.RESULTSIcodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC_0-t: ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (C_max): 1.12 [1.06; 1.18]. Semaglutide AUC_0-t was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide C_max was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone.CONCLUSIONThe combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema.CLINICAL TRIALClinicalTrials.gov identifier: NCT03789578.

News (Medical) associated with Icodec Insulin/Semaglutide

06 Sep 2024

·www.novonordisk.com

Novo Nordisk to present new data from key diabetes and obesity trials at the 60th annual meeting of the European Association for the Study of Diabetes

Bagsværd, Denmark, 6 September 2024 – Novo Nordisk today announced the presentation of 21 abstracts (7 oral and 14 short oral presentations) at the upcoming 60 th Annual Meeting of the European Association for the Study of Diabetes (EASD), which will take place from 9 to 13 September 2024 in Madrid, Spain. In addition to the abstracts, data will also be presented in dedicated scientific symposia. These include results from the COMBINE clinical programme with IcoSema, a combination of once-weekly basal insulin icodec and once-weekly semaglutide, in people with type 2 diabetes, the FLOW trial evaluating semaglutide 1.0 mg on kidney outcomes in people with type 2 diabetes and chronic kidney disease, and amylin treatment for metabolic disease. “Cardiometabolic conditions like diabetes, obesity, cardiovascular and kidney disease, all result from closely interlinked underlying risk factors and are among the most significant health challenges society faces today. Tailored treatment options that aim to holistically address these conditions are therefore needed,” said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. “At EASD this year, we are showcasing new data from across our diabetes, obesity, cardiovascular and renal pipeline and portfolio, where we continue to push boundaries with the goal of advancing treatments in order to help more patients.” Summary of presentations Accepted data at the 60 th annual meeting of the EASD include the following oral and short oral presentations. Accepted abstracts include preliminary data that may be subject to change in final published manuscripts. Dates and times of the presentations and the abstracts can be found on the EASD website . EASD scientific symposia EASD oral and short oral presentations Diabetes Awiqli ® (once-weekly basal insulin icodec) Ozempic ® (once-weekly semaglutide 1.0 mg) Non-product Obesity Wegovy ® (once-weekly semaglutide 2.4 mg) Saxenda ® (once-daily liraglutide 3.0 mg) Oral amycretin CagriSema Digital Health About Awiqli ® (once-weekly basal insulin icodec) Awiqli ® (once-weekly insulin icodec) is a novel once-weekly basal insulin analogue designed to cover the basal insulin requirements for a full week with a single subcutaneous injection. In the EU, Awiqli ® is indicated for the treatment of diabetes mellitus in adults. About Ozempic ® (semaglutide 1.0 mg) In the EU, Ozempic ® is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance or contraindications, or in addition to other medicinal products for the treatment of diabetes. About Wegovy ® (semaglutide 2.4 mg) In the EU, Wegovy ® is indicated as an adjunct to a reduced calorie diet and increased physical activity for weight management in adults with a BMI of 30 kg/m 2 or greater (obesity), or adults with a BMI of 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition. In the EU, Wegovy ® is also indicated for paediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and gender (obesity) and body weight above 60 kg. About Saxenda ® (liraglutide 3.0 mg) In Europe, Saxenda ® is indicated along with diet and increased physical activity for weight management in adults with a BMI of 30 kg/m 2 or greater (obesity), or adults with a BMI of 27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition. Saxenda ® is also indicated for adolescents from 12 years of age with obesity (BMI of 30 kg/m 2 or more) who weigh more than 60 kg. About Novo Nordisk Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 69,000 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com , Facebook , Instagram , X , LinkedIn and YouTube . Contacts for further information

Drug Approval

13 Aug 2024

·www.fiercepharma.com

CORRECTED: After icodec rejection, Novo Nordisk won't file application for once-weekly insulin and semaglutide combo in US

IcoSema is a combination of once-weekly insulin icodec and once-weekly semaglutide for the treatment of Type 2 diabetes. Semaglutide is the molecule underpinning Novo’s immensely popular GLP-1 drugs Ozempic and Wegovy. As Novo Nordisk moves full speed ahead on global regulatory filings for a combination of once-weekly insulin icodec and semaglutide, the U.S. won’t be part of that plan, for now, thanks to a recent regulatory hiccup with the FDA. Following a positive readout in the late-stage COMBINE 1 trial, Novo is planning to submit applications for IcoSema during the second half of 2024, Martin Holst Lange, M.D., Ph.D., executive vice president of development at Novo Nordisk, said on a recent analyst call.Still, the company won’t be able to file in the U.S. given that icodec, the insulin component of the combination Type 2 diabetes candidate, was recently slapped with a complete response letter by the FDA, a company spokesperson told Fierce.IcoSema is a combination of once-weekly insulin icodec and once-weekly semaglutide for the treatment of Type 2 diabetes. Semaglutide is the molecule underpinning Novo’s immensely popular GLP-1 drugs Ozempic and Wegovy. Icodec has been approved as Awiqli in places like Europe, Canada, Japan and Australia but was snubbed by the FDA last month.In its rejection, the U.S. agency made “requests related to the manufacturing process and the type 1 diabetes indication,” Novo said at the time. The company said it didn’t expect to remedy the issues before 2024 is out.The rejection came about seven weeks after an FDA panel of outside experts recommended against approving the once-a-week insulin product, raising questions about icodec’s risk of causing low blood sugar.As for the data the company will leverage to seek approval for IcoSema elsewhere, Novo’s COMBINE 1 study sought to assess the safety and efficacy of switching to once-weekly IcoSema from once-weekly insulin icodec in Type 2 diabetes patients whose disease was inadequately controlled on daily basal insulin with or without oral diabetes drugs.Ultimately, IcoSema proved superior at reducing A1c—a measure of a patient’s blood sugar over time—compared to insulin icodec at the trial’s 52-week mark, meeting the study’s primary objective, Lange told investors last week.From an overall HbA1c base line of 8.2%, IcoSema helped patients reduce their A1c by 1.6% versus 0.9% with insulin icodec, the executive explained.Treatment with IcoSema also helped patients lose around 3.7 kg (8.2 pounds) versus a 1.9-kg (4.2-pound) weight gain for patients on insulin icodec.Further, patients on IcoSema experienced a “typically significantly lower” rate of major hypoglycemia events (0.14 events per patient years of exposure) versus insulin icodec (0.63 events per patient year of exposure), according to Lange.The executive added that IcoSema appeared to be safe and well tolerated. Meanwhile, Novo’s chief rival in diabetes and weight loss, Eli Lilly, is testing its own once-weekly insulin.In May, Lilly unveiled data from a pair of phase 3 studies showing its candidate, efsitora alfa, was noninferior to daily insulin at 52 weeks, with patients’ A1c falling 1.34% and 1.26%, respectively. Editor's note: This story replaces a previous version that incorrectly stated Novo Nordisk would be filing for approval of IcoSema in the U.S. this year.

Drug ApprovalClinical ResultPhase 3

12 Aug 2024

·firstwordpharma.com

Novo Nordisk targets filing this year for insulin, GLP-1 combo IcoSema

After the FDA's recent snub of its once-weekly basal insulin Icodec, Novo Nordisk is forging ahead with plans to file for US approval of IcoSema, a combination treatment pairing Icodec with the company's GLP-1 agonist semaglutide. The decision follows positive results from the late-stage COMBINE 1 trial."Now that the third and last pivotal Phase III trial is completed, we expect to file for regulatory approval of IcoSema during the second half of 2024," stated Martin Holst Lange, Novo's head of development, during a recent analyst call. IcoSema is also being evaluated in the Phase III COMBINE 2 and COMBINE 3 trials.COMBINE 1 compared once-weekly IcoSema to once-weekly Icodec in type 2 diabetes patients whose disease was inadequately controlled on daily basal insulin, regardless of whether they were on any oral diabetes meds. According to Lange, the trial achieved its primary endpoint with IcoSema demonstrating superiority over Icodec at reducing HbA1c at 52 weeks.Specifically, from an overall HbA1c baseline of 8.2%, Lange said IcoSema led to an estimated reduction in HbA1c of 1.6 percentage points compared to 0.9 percentage points for Icodec. IcoSema also showed better weight loss effects, with patients losing 3.7 kg compared to a 1.9-kg weight gain in the insulin Icodec group. People in the trial had a baseline body weight of 84.5 kg.The combination treatment showed a favourable safety profile as well. "The rate of clinically significant or severe hypoglycaemia was typically significantly lower with IcoSema at 0.14 events per patient years of exposure, versus 0.63 events per patient year of exposure with once-weekly insulin Icodec," Lange reported.The news comes on the heels of the FDA's rejection of Icodec as a standalone treatment last month. Lange addressed the setback, saying "we're evaluating the content of the CRL [complete response letter], and we'll work closely with the FDA to fulfill their requests. We do not expect to be able to fulfill the request during 2024." The CRL sought additional data relating to Icodec's manufacturing process and its use in people with type 1 diabetes.

Phase 3Clinical Result

100 Deals associated with Icodec Insulin/Semaglutide

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 3	FR	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	TH	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	TR	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	ZA	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	MY	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	HU	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	IN	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	IT	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	SI	Novo Nordisk A/S	30 Nov 2021
Diabetes Mellitus, Type 2	Phase 3	US	Novo Nordisk A/S	30 Nov 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05259033 (COMBINE 2, CTgov)	Phase 3	Diabetes Mellitus, Type 2	683	IcoSema (IcoSema)	(gdrwfjtzua) = lvqctdnwts znmdwedgnk (ujuumvkdll, ibhrzqsdrv - ghbjcqrjbp) View more	-	17 Jan 2025
				Semaglutide 1 mg (Semaglutide)	(gdrwfjtzua) = aauwedlkzj znmdwedgnk (ujuumvkdll, fysikayzao - udsnstjkpz) View more

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