In 2023, Non-Alcoholic Steatohepatitis (NASH) was officially reclassified as Metabolic Associated Steatohepatitis (MASH). With the emergence of 'Resdipra' in 2024, the liver and metabolic disease sector has become a key battleground in the global pharmaceutical industry. Unmet needs in high-risk patient groups have been reaffirmed, particularly in the US and Europe, prompting major pharmaceutical companies to realign their next-generation growth strategies towards liver and metabolic diseases and accelerate aggressive acquisition and licensing strategies. The demand for fibrosis improvement has increased, intensifying competition in the development of multi-mechanism-based therapies, rapidly reshaping the market.

Global Pharmaceutical Companies Focus on Third-Generation MASH Therapy FGF21

The development of MASH therapies has transitioned from first-generation THR-β-based to second-generation incretin-based therapies like GLP-1, and is now moving towards third-generation 'FGF21 class' therapies. FGF21 (Fibroblast Growth Factor 21) is an endocrine hormone that extensively regulates liver, fat, and muscle metabolism while inhibiting inflammation and fibrosis, enhancing its technological value by targeting overall liver diseases. Its multi-mechanistic superiority, including liver fat improvement, fibrosis reduction, and liver function recovery, is presented as an advantage over existing therapies.

Particularly, while existing approved drugs have shown limited efficacy primarily in fibrosis stages 1 to 3, recently developed FGF21 analogs have demonstrated potential histological improvements even in fibrosis stages 3 to 4, i.e., severe fibrosis and early cirrhosis patients, highlighting them as alternatives in areas lacking treatment options.

In 2025, major deals have concentrated around FGF21-based assets. GlaxoSmithKline (GSK) announced an acquisition involving an upfront payment of USD 1.2 billion (approximately KRW 1.7626 trillion) and up to USD 2 billion (approximately KRW 2.9378 trillion) to secure the long-acting FGF21 analog 'Epfimospermin Alpha.' Roche acquired 89bio, which holds the late-stage clinical 'Pegozafermin,' for approximately USD 2.4 billion (up to USD 3.5 billion), while Novo Nordisk acquired Akero Therapeutics to secure 'Efursifermin (EFX)' for an upfront payment of USD 4.7 billion (KRW 6.9038 trillion) and up to USD 5.2 billion (approximately KRW 7.6382 trillion).

Over USD 10 billion (approximately KRW 14.688 trillion) has been invested in the FGF21 class in 2025 alone, forming a consensus in the global pharmaceutical industry that FGF21 will become a core pillar of future MASH standard therapies. The three factors of multi-mechanism, late-stage clinical phase, and high-risk patient group efficacy are positioning the FGF21 platform as a 'third-generation integrated metabolic and liver disease therapy.'

Yuhan Corporation Leads Domestically with Dual-Action Agent YH25724

In Korea, the development of liver and metabolic disease therapies is expanding, but among candidates with MASH set as the primary indication and global clinical data, Yuhan Corporation's 'YH25724' is evaluated as the only MASH-specialized pipeline.

YH25724 boasts a dual structure of FGF21 and GLP-1, simultaneous improvement of fatty liver and fibrosis in preclinical studies, completion of global Phase 1 trials in the US, Europe, and Japan, and early clinical experience with multinational pharmaceutical companies, providing a competitive edge. The combined mechanism of FGF21's fatty liver improvement and fibrosis inhibition with GLP-1's weight loss and metabolic regulation effects complements the limitations of existing single incretin-based therapies.

Additionally, the platform's potential for expansion into various indications such as obesity, MASLD, MASH, and fibrosis aligns precisely with the recent global trend favoring multi-action agents. Consequently, the potential for re-evaluation of technological value and expansion of overseas partnerships is highly anticipated.

Yuhan Corporation's development of the FGF21-GLP-1 dual-action agent as the first in Korea is expected to be an important stepping stone in expanding global new drug competitiveness, following the non-small cell lung cancer treatment 'Lecraza.' It is also significant as the first case of a Korean company entering the global technology platform competition in the liver and metabolic disease sector.

Since the reclassification of diseases to MASH, the global pharmaceutical industry has focused on multi-mechanism therapies encompassing fibrosis improvement, with the FGF21 class at the center. As confirmed by the major acquisitions of GSK, Roche, and Novo Nordisk, FGF21 is emerging as a core pillar of future standard therapies. Domestically, Yuhan Corporation is closest to the global competitive landscape with its FGF21-GLP-1 dual-action agent YH25724, with high expectations for future technology exports and expanded overseas collaborations.

As the treatment paradigm for liver and metabolic diseases enters the third-generation phase, FGF21-based therapies are positioning themselves as strong candidates to resolve the long-standing limitation of lacking treatment options in high-risk groups. The strategic value of the FGF21 platform is expected to grow further in both global and domestic markets.

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