Obesity Surge: Pharma Boom Ahead?

"Obesity is gradually eroding human health," and it is estimated that by 2035, the global prevalence of obesity (BMI ≥ 30) will reach 25%, affecting approximately 1.9 billion people. With the continuous increase in the obese population, the demand for drugs to prevent and treat related diseases continues to rise. In response to this "new normal" of obesity, many companies are actively making layouts, such as Pfizer, Novartis, and Eli Lilly, which are increasing their R&D investments to develop more effective solutions to address the obesity crisis.

Global obesity prevalence rate (source: world obesity atlas 2023)

GLP-1 Related Drugs Boom, Pain Points Urgent

Wegovy® is the first FDA-approved weight-management medication, designed to mimic glucagon-like peptide-1 (GLP-1) – a hormone that targets areas in the brain responsible for regulate appetite and food intake. It Its approval signifies a major milestone in the rapid growth of the GLP-1 anti-obesity drug market.

Figure of Wegovy®

However, behind this booming development, GLP-1 weight loss drugs also face crucial pain points that require urgent attention: long-term use of GLP-1 drugs may lead to muscle loss. In response, the industry has embarked on a new round of layout in the obesity treatment sector, with several pharmaceutical companies targeting other new therapeutic targets, such as the Activin receptor Activin R, in hopes of developing innovative therapies that can effectively reduce weight while protecting muscles.

Emerging Target for Fat Loss and Muscle Gain: Activin R

Activin belongs to the TGF-β superfamily and plays a crucial role in regulating various physiological processes such as cell proliferation, differentiation, and apoptosis. In muscle tissue, Activin binds to its receptor Activin RII, activating intracellular signaling pathways. Activin RII phosphorylates Activin RI, subsequently activating the Smad2/3 signaling pathway. The activated Smad2/3 transcription factors enter the nucleus and regulate the expression of genes related to muscle protein metabolism. The proteins encoded by these genes are involved in inhibiting protein synthesis and activating protein degradation, ultimately leading to muscle atrophy. Therefore, inhibiting the Activin signaling pathway may achieve efficient fat reduction.

The signaling pathway of Activin

The development of targeted drugs targeted Activin R offers new therapeutic strategies for the treatment of sarcopenia, metabolic diseases, and other conditions. Bimagrumab, LAE102, and Garetosmab are three representative monoclonal antibody drugs targeting Activin.

- Bimagrumab developed by Novartis, is a high-affinity antibody targeted Activin RIIB that can block the Activin signaling pathway and promote muscle growth. Nunn's research found that during semaglutide treatment, the use of Bimagrumab can maintain lean body mass while increasing the reduction of fat mass, and this maintenance of lean body mass is associated with improvements in metabolic and functional outcomes.

- On June 26, 2024, Laekna, Inc announced that the first patient enrollment and successful dosing in the Phase I clinical trial of its self-developed LAE102 (a monoclonal antibody against Activin RIIA) for the treatment of overweight/obesity in China has been completed at Zhongshan Hospital, Fudan University, Shanghai.

- Garetosmab, developed by Regeneron Pharmaceuticals, is a fully human IgG4 monoclonal antibody that, unlike Bimagrumab and LAE102, primarily targets Activin A associated with muscle growth. Publicly announced trials combining Garetosmab with semaglutide, set to commence in May, aim to explore solutions for enhancing weight loss quality and preventing rebound after discontinuation of treatment. Currently, no progress has been disclosed.

As Activin R-targeting drugs gradually enter clinical application, they have the potential to become the key to addressing the current pain points of GLP-1-based weight loss medications. New drugs based on Activin R are poised to emerge as ideal options that balance weight loss and muscle gain, making a mark in the future obesity treatment market.

ACROBiosystems provides a series of Activin receptor proteins with high biological activity verified by ELISA and affinity confirmed through SPR&BLI. These proteins can be widely used in Activin-related pathway research and targeted drug development, facilitating the exploration of the regulatory mechanisms of Activin pathways in obesity and muscle metabolism.

Activin Family: An Emerging Target for Disease Treatment

Beyond applications in obesity, members of the Activin family, such as Activin A and Activin B, have also demonstrated extensive therapeutic potential in various other diseases, including liver fibrosis, renal diseases, neurological disorders, and immune diseases.

Diseases associated with Activin signaling pathways

ACROBiosystems can provide you with a comprehensive range of Activin family proteins, including Premium-grade Activin products for cell culture, fueling the continuous exploration of innovative therapeutic solutions.

>> Cytokine Targets for Developing Therapeutics

>> Growth Factors for Cell Culture

Reference

1. Nunn E, Jaiswal N, Gavin M, et al. Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism[J]. Molecular Metabolism, 2024, 80: 101880.

2. Wang Y, Nguyen J H, de Ruiter R D, et al. Garetosmab in Fibrodysplasia Ossificans Progressiva: Clinical Pharmacology Results from the Phase 2 LUMINA‐1 Trial[J]. The Journal of Clinical Pharmacology, 2024, 64(2): 264-274.

3. Zhang Y. Fat Loss and Muscle Gain: Targeting the Activin Signaling Pathway[J].

4. Lodberg, Andreas. "Principles of the activin receptor signaling pathway and its inhibition." Cytokine & Growth Factor Reviews 60 (2021): 1-17.

5.  IQVIA Thought Leadership; World Obesity Federation, World Obesity Atlas 2023.