Exploration of Digestive Diseases

Table 1. List of ongoing pharmacotherapeutic agents in phase II–IV trials for MASH/MASLD

Target		Agent	Latest phase	NCT	Sponsor
Nuclear receptor agonists	THRβ agonist	Resmetirom	FDA-approved	NCT04951219 NCT04197479 NCT05500222 NCT03900429	Madrigal Pharmaceuticals
		VK2809	Phase II	NCT04173065 NCT02927184	Viking Therapeutics
		ASC41		NCT05462353	FirstWord Pharma
		TERN-501		NCT05415722	Terns Pharmaceuticals
	PPARα/δ/γ agonist	Pioglitazone	Phase IV	NCT00994682	University of Florida
		IVA337 (Lanifibranor)	Phase III	NCT04849728 NCT05232071 NCT03459079	Inventiva Pharma
		Elafibranor	Phase III	NCT02704403 NCT03883607 NCT01694849	Genfit
		Saroglitazar	Phase II	NCT03061721 NCT03863574	Zydus Therapeutics
		Pemafibrate	Phase II	NCT05327127 NCT03350165	Kowa Research Institute, Inc.
	FXR agonist	Obeticholic acid	Phase III	NCT02548351 NCT01265498	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
		Cilofexor	Phase II	NCT02854605	Gilead Sciences
		HPG1860		NCT05338034	Hepagene (Shanghai) Co., Ltd.
		Tropifexor		NCT02855164 NCT04147195 NCT03517540	Novartis Pharmaceuticals
		TERN-101		NCT04328077	Terns, Inc.
		MET409		NCT04702490	Metacrine, Inc.
		CS0159		NCT05591079	Cascade Pharmaceuticals, Inc
GLP-1R agonist		Semaglutide		NCT04822181 NCT02970942	Novo Nordisk A/S
		Liraglutide		NCT01237119 NCT02654665	University of Birmingham
		Dulaglutide	Phase IV	NCT03648554	Central Hospital, Nancy, France; Eli Lilly and Company
A3 adenosine receptor agonist		Namodenoson	Phase III	NCT02927314	Can-Fite BioPharma
FGF mimetics	FGF21 analogue	Efruxifermin	Phase III	NCT06215716 NCT06161571 NCT03976401 NCT04767529	Akero Therapeutics
FGF mimetics	FGF21 analogue	Pegozafermin	Phase II	NCT03486912 NCT03486899 NCT03400163 NCT02413372	89bio
Inhibitors	SCD-1 inhibitor	Aramchol	Phase III	NCT04104321	Galmed Research and Development
	CCR2/CCR5 inhibitor	Cenicriviroc		NCT03028740	Tobira Therapeutics, Inc.
	Galactin-3 inhibitor	Belapectin (GR MD-02)		NCT06035874	Galectin Therapeutics
	ASK1 inhibitor	Selonsertib		CTR20230344	The First Hospital of Jilin University
	ACC inhibitor	GS-0976		NCT02856555	Gilead Sciences
	ACC inhibitor	MK-4074		NCT01431521	Merck Sharp & Dohme LLC
	FASN inhibitor	Denifanstat		NCT04906421	Sagimet Biosciences Inc.
	MPC inhibitor	MSDC-0602K		NCT02784444	Cirius Therapeutics, Inc.
	ACLY inhibitor	Bempedoic acid		NCT06035874	Medanta - The Medicity
	ACLY inhibitor	BGT-002		CTR20230344	The First Hospital of Jilin University
Combination therapy	ACC inhibitor DGAT2 inhibitor	PF-05221304 PF-06865571	Phase III	NCT04321031 NCT03248882 NCT03776175	Pfizer
	ASK1 inhibitor ACC inhibitor FXR agonist	Selonsertib Firsocostat Cilofexor		NCT02781584	Gilead Sciences
	FXR agonist HMGCR inhibitor	Obeticholic acid Atorvastatin		NCT02633956	Intercept Pharmaceuticals
	FXR agonist GLP-1R agonist	Cilofexor Semaglutide		NCT03987074	Gilead Sciences

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MASLD: metabolic dysfunction-associated steatotic liver disease; THRβ: thyroid hormone receptor β; PPARα/δ/γ: peroxisome proliferator-activated receptor α/δ/γ; FXR: farnesoid X receptor; GLP-1R: glucagon-like peptide-1 receptor; FGF: fibroblast growth factor; SCD-1: stearoyl-CoA desaturase-1; CCR2/CCR5: C-C chemokine receptor type 2/5; ASK1: apoptosis signal-regulating kinase 1; ACC: acetyl-CoA carboxylase; FASN: fatty acid synthase; MPC: mitochondrial pyruvate carrier; ACLY: ATP-citrate lyase; DGAT2: diacylglycerol O-acyltransferase 2; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase

Declarations

Acknowledgments

During the preparation of this work, the authors used GPT-4o (San Francisco, USA) in order to improve language. After using this tool/service, all authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Author contributions

JW and JL: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MCH and HM: Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

Prof. Han Moshage is an Associate Editor of Exploration of Digestive Diseases. However, he was not involved in any aspect of the peer review or editorial decision-making process for this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This project is financially supported by the China Scholarship Council, File No. [202006250036] (J.W.) & No. [202106200024] (J.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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