Novo Nordisk Shares Early Findings for Novel Oral Antiobesity Agent

_{©JHVE photo/stock.adobe.com}

A novel investigational oral antiobesity drug from Novo Nordisk reportedly returned weight reduction of 13.1% over just 12 weeks in a small phase 1 clinical trial, according to details released during the company’s annual capital markets day in Copenhagen today.¹

Amycretin, a combined unimolecular glucose-like peptide 1 (GLP-1) and amylin agonist, was observed to be safe and well tolerated with side effects similar to other GLP-1 receptor agonists indicated for treatment of obesity, according to a presentation made at the meeting.¹

The 13% weight loss seen in this early-stage study is more than double the reduction of 6% Novo reported at 12 weeks for its first antiobesity agent, the subcutaneous GLP-1 mimetic semaglutide (Wegovy).

Amylin and GLP-1 are endocrine peptide hormones that have a dual role in appetite regulation and glucose control and have complementary mechanisms of action. Amylin is also involved in body composition and bone homeostasis, according to the company's presentation.¹

It is important to note that the current results have not been subject to peer review, published in a scientific journal, or presented at a scientific meeting.

While the phase 1 study was small, the company said the amycretin pharmacokinetic profile supports further clinical development. Speaking with Forbes,² Martin Lange Holst, Novo head of development, said that the promising results justify further research and that the company will begin a larger phase 2 trial in the second half of 2024. Results of that mid-stage study are expected in early 2026, according to Holst.² Novo is also testing a subcutaneous form of amycretin in an ongoing early stage trial with data expected to be released in 2025.¹

“At the very least amycretin has the potential of showing the same efficacy and safety as CagriSema and we have the ability to bring that to patients in either an oral or subcutaneous format,” Holst said in an interview today with Endpoint News.³ “We’re currently investigating the subcutaneous format [of amycretin] in Phase I that will read out sometime in 2025 and then we’ll look at the data and we will figure out how to go into what I would call an ambitious further development program,” he explained.³

Novo's CagriSema is a fixed dose combination of GLP-1 RA semaglutide (2.4 mg) and cagrilintide (2.4 mg), the latter a long-acting amylin analogue that potentiates the weight loss effects of semaglutide.¹ In phase 2 findings the combination was linked to a decrease in body weight of 15.6% from baseline at week 32. In November 2023, Novo announced the launch of a phase 3 trial that will directly compare the safety and efficacy CagriSema to the maximum dose of Eli Lilly’s tirzepatide (Zepbound) for weight loss.⁴

In the meeting presentation, Novo highlighted additional phase 1 trials planned for initiation over the next 12 months including a new amylin molecule for monotherapy that could be promising for weight management and has the potential for combining with molecules with complementary or additive properties.¹ A novel tri-agonist is also slated to enter an early-stage trial, a combination Novo said has the potential for improved weight loss efficacy as well as improved effects on comorbidities associated with overweight and obesity. The company did not specify the type of molecules.

References

1. Schindler M. (2024). Research and early development. Capital markets day 2024. PowerPoint slideshow. Novo Nordisk. March 7, 2024. Copenhagen, Denmark. Accessed March 7, 2024. https://cdn.evenzu.io/event/hxr1zomb2k05vitfdy6lsua3j7c8pe9n/file/evev269_d1709793399.pdf

2. Hart R. Novo Nordisk’s new obesity pill beats Wegovy in early trial. Forbes. March 7, 2024. Accessed March 7, 2024. https://www.forbes.com/sites/roberthart/2024/03/07/novo-nordisks-new-obesity-pill-beats-wegovy-in-early-trial/

3. Lewin K, Tong A. Novo touts early data for next-gen oral weight loss drug as it outlines next steps. Endpoint News. March 7, 2024. Accessed March 7, 2024. https://endpts.com/novo-reports-early-weight-loss-data-for-amycretin-outlines-next-steps/

4. Novo Nordisk launches trial of pipeline drug CagriSema versus newly approved Zepbound. Clinical Trials Arena. November 17, 2023. Accessed March 7, 2024. https://www.clinicaltrialsarena.com/analyst-comment/novo-nordisk-cagrisema-versus-zepbound/?cf-view