Novo Nordisk Unveils Breakthrough Oral Weight-Loss Drug Amycretin, Surging Market Cap Beyond $600 Billion

Mar 08, 2024 21:45 CST Updated 21:45

Novo Nordisk

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On 2024-03-08, Novo Nordisk held the Capital Markets Day 2024 (CMD) event. During the event, presentations by Novo Nordisk's senior management covered corporate strategy and goals with sustainability (ESG), research and early development, product offerings in diabetes, obesity, and rare diseases, as well as the R&D pipeline and performance.

Figure 1. Novo Nordisk CMD2024 Overview

Most importantly, CMD introduced a series of the latest pipeline advancements by Novo Nordisk in the currently booming obesity field. The key pipeline drugs include the combination therapy CagriSema, CB1R inverse agonists INV-202 and INV-347, and the重磅 experimental new drug Amycretin, showcasing to the industry what "one mountain is higher than the other" truly means.

Figure 2. Novo Nordisk CMD2024 Pipeline Drug Display

Novo Nordisk CMD Triggers Secondary Market Fluctuations: Novo Nordisk Surges Nearly 9%, Market Cap Breaks $600 Billion, Lilly Stock Remains Flat; Viking Shares Plunge 18.84% Following Stunning Clinical Data Release Days Ago.

Figure 3. Novo Nordisk/Lilly/Viking Stock Price Changes

（2024-03-07）

Dual-Target New Drug Amycretin Shows Stunning Efficacy

Novo Nordisk announced the GLP-1+Amylin dual agonist Amycretin, which is being developed in two formulations: oral (NN9487) and subcutaneous injection (NN9490). This meeting disclosed the preliminary Phase I clinical data for oral Amycretin, with Phase I data for the subcutaneous formulation expected to be available in 2025.

Figure 4. Schematic diagram of Amycretin structure

Phase I clinical data of oral Amycretin showed that patients lost an average of 13.1% of their weight within 12 weeks, with a continued downward trend.

Figure 5. Amycretin Phase I Clinical Data

What is the weight loss efficacy of oral Amycretin? Compare with oral GLP-1R drugs: In the Phase III trial, the highest dose group of 50mg oral Semaglutide achieved a weight loss of approximately 5% in 12 weeks, while the Phase II trial of 45mg Orforglipron showed a weight loss of about 8% in 12 weeks.Oral Amycretin showed better efficacy compared to small-molecule, single-target peptide oral medications over a 12-week period.

Figure 6. Semaglutide/Orforglipron Clinical Data

Comparison of GLP-1R Injectable Drugs: Tirzepatide Phase III 15mg Maximum Dose Group Achieves Approximately 7% Weight Loss, Retatrutide Phase II 12mg Dose Group Achieves Approximately 12% Weight Loss, Viking's VK2735 15mg Dose Group Achieves Approximately 14.7% Weight Loss in 13 Weeks, and Amgen's Phase I AMG-133 420mg Dose Group Achieves a 14.5% Reduction in Body Weight After 12 Weeks.Oral Amycretin shows significant short-term efficacy compared to Tirzepatide and Retatrutide, while long-term weight loss effects need further data validation; its early efficacy is similar to VK2735 and AMG-133, but the oral form enhances patient compliance.

Figure 7. Tirzepatide/Retatrutide/VK2735/AMG-133 Clinical Data

Although results are difficult to compare across different clinical trials, the rapid weight loss effect shown in the early results of Amycretin's Phase I trial demonstrates the drug's significant potential. Therefore, some analysts have described it as one of the best weight-loss drugs tested to date.

CagriSema Data Released

Unlike the dual-target compound Amycretin, CagriSema is a combination of Cagrilintide and Semaglutide, with the highest dose group being 2.4mg Cagrilintide + 2.4mg Semaglutide.

Cagrilintide, developed by Novo Nordisk, is an Amylin analog that is a compound based on human Amylin with chemical structure modifications and the addition of a fatty chain, having a half-life of 159~195 hours.

Figure 8. Cagrilintide Sequence

Cagrilintide itself functions by directly acting on the brain to suppress appetite, slow down intestinal digestion, and inhibit the production of GCG glucagon. The combination of Cagrilintide and GLP-1 can bring about a good synergistic effect.

Figure 9. AMylin and GLP-1 Synergistic Effects

Novo Nordisk Announces Positive Results of CagriSema in a 20-Week Phase I Trial: CagriSema Led to a 17.1% Weight Reduction in Patients, Compared to Only 9.8% in the Semaglutide Group. Currently, Five Phase III Clinical Trials Related to CagriSema Are Underway.

Figure 10. CagriSema Clinical Progress

Other Clinical Progress

Novo Nordisk announced the Phase I study results of CB1R inverse agonist Monlunabant, showing that by Day 28, the Monlunabant group had an average weight loss of 3.5 kg (3.3%), while the placebo group gained 0.6 kg (0.5%).Monlunabant has good safety and tolerability, with the most common side effects being gastrointestinal reactions. As an oral small molecule, Monlunabant’s effectiveness in weight loss is highly anticipated.

Figure 11. Monlunabant Clinical Progress

On August 10, 2023, Novo Nordisk acquired the Canadian company Inversago Pharma, gaining its clinical-stage pipeline for the treatment of obesity, diabetes, and other metabolic disorders. This acquisition includes multiple pipelines from Inversago, such as INV-202, a CB1r inverse agonist in Phase II clinical trials, used to treat diabetic nephropathy, metabolic syndrome, and other diseases. Novo Nordisk will pay $600 million as an upfront payment, with the total deal potentially reaching up to $1.075 billion if milestones are achieved.

In addition to Monlunabant, Novo Nordisk also presented the clinical development plans for GLP-1+GIP dual-target drugs, new Amylin drugs, and new triple-target weight loss drugs.