Nonalcoholic Steatohepatitis (NASH) Market to Observe Stunning Growth by 2032 Owing to a Robust Pipeline

The NASH market is expected to evolve because of emerging therapies like MGL-3196, Semaglutide, Vonafexor, HPG1860, VK2809, BIO89-100, LPCN 1144, and others. 

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States. It’s estimated that about 25% of adults in the US have NAFLD, and of those about 20% have NASH (5% of adults in the US). Presently, there are no FDA, EMA, or PMDA-approved therapies for the treatment of NASH, however, emerging therapies such as MGL-3196, Semaglutide, Lanifibranor/IVA337, MSDC-0602K, Vonafexor (EYP001), and others are showing good results. The current front-line treatment consists of lifestyle modifications, such as diet and exercise. Additional treatment options for NASH, aside from lifestyle modifications, have included off-label use of vitamin E and anti-diabetes agents (e.g., pioglitazone and liraglutide).

To know more about upcoming nonalcoholic steatohepatitis therapies showing positive results, visit @ NASH Treatment Drugs

As per DelveInsight analysis, the NASH market size is supposed to grow at a significant CAGR during the forecast period owing to the expected launch of novel emerging therapies, which shall fuel the growth of the NASH market during the forecast period, i.e., 2023–2032. As per the estimates, the United States accounts for the highest market size of the total NASH market size in 7MM in 2022, in comparison to the other major markets i.e., EU5 countries (the United Kingdom, Germany, Italy, France, and Spain), and Japan.

The current NASH pipeline consists of a great deal of drugs. FXR Agonists, FGF21 Stimulants, FGF19 Analog, Glucagon-like Peptide-1 (GLP-1) Agonist, Peroxisome Proliferator-activated Receptor (PPAR) Regulator, THR-β Agonist, and some others are the most highlighted class of this indication. Ongoing research and current trials have the potential to change the NASH market.

Other targets for NAFLD and NASH therapy include G protein-coupled receptors (GPCRs), estrogen-related receptor alpha (ERRα), bone morphogenetic proteins (BMPs), and KLFs. The NASH market is quite void due to the lack of any approved medication; there is a big need for NASH treatment. 

Keen to know how the NASH market will evolve by 2032? Find out @ NASH Market Forecast

The potential for effective NASH treatment in the future is expected to grow with the addition of numerous drugs to the pipeline of new therapeutics. Currently, a variety of candidate drugs for the treatment of NASH are being tested in phase II or III clinical trials, with some showing positive results. Any drug approved with increased safety and efficacy is expected to cause significant changes in the overall NASH market.

Now, let’s examine the mid and advanced-stage therapies under investigation for NASH

MGL-3196 (Resmetirom): Madrigal Pharmaceuticals, Inc.

Phase III

MGL-3196 (Resmetirom) is a liver-directed, orally active, selective thyroid hormone receptor-β agonist designed by Madrigal Pharmaceuticals, Inc. to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity. Essentially, this drug’s primary mechanism of action suggests potentially improving the patient’s lipid profile and hepatic fat. In July 2016, Madrigal Pharmaceuticals, Inc. merged with Synta Pharmaceuticals Corp. to advance its research and development efforts, including the clinical development of MGL-3196, Madrigal’s lead product candidate. The FDA granted resmetirom Breakthrough Therapy designation in April 2023 for the treatment of adults with NASH and liver fibrosis.

In December 2022, Madrigal announced topline results from the pivotal Phase III MAESTRO-NASH biopsy study of resmetirom. Madrigal reported that resmetirom achieved both primary endpoints with both daily oral doses, 80 mg, and 100 mg, relative to placebo. The positive readout from the Phase III clinical trials marks a significant turning point for the field. MAESTRO-NAFLD-1 will advance noninvasive imaging and biomarkers in NASH drug development because it is the first Phase III study in NASH that does not rely on liver biopsy to identify patients and gauge treatment response. This drug is unique among NASH drugs under development that reduces cardiovascular risk by reducing liver fat and lowering the levels of some atherogenic lipids, including LDL cholesterol, on a scale consistent with approval for dyslipidemia. The development in clinical trials was not interrupted during the pandemic, and its positive safety and efficacy results make it a promising drug candidate.

Recently, Madrigal Pharmaceuticals completed the submission of a new drug application seeking accelerated approval of resmetirom for the treatment of NASH with liver fibrosis. The drug is expected to launch in 2024 in the US.

Semaglutide: Novo Nordisk A/S

Phase III

Semaglutide, a lead product of Novo Nordisk A/S also a GLP-1 analogue indicated for T2D, is under evaluation for both weight management and NASH treatment, and has been shown to significantly reduce alanine aminotransferase (ALT) and high sensitivity C-reactive protein (hsCRP) in a dose-dependent manner in patients with obesity or T2D in its phase III trials. The drug received the Breakthrough Therapy designation by the FDA in August 2020 for NASH. In June 2023, Merck’s GLP-1/glucagon receptor co-agonist won the FDA’s Fast Track designation for NASH treatment.

In 2015, Gilead Sciences, Inc. announced the acquisition of Phenex Pharmaceuticals’ FXR program comprising small molecule FXR agonists (cilofexor) for treating liver diseases, including NASH. In 2016, Gilead Sciences, Inc. and Nimbus Therapeutics signed a definitive agreement under which Gilead will acquire Nimbus Apollo, Inc., a wholly owned subsidiary of Nimbus Therapeutics, and its ACC inhibitor (firsocostat) program for NASH and other liver diseases.

In November 2021, Gilead Sciences and Novo Nordisk expanded NASH clinical collaboration. The companies will conduct a Phase IIb double-blind, placebo-controlled study to investigate the safety and efficacy of Novo Nordisk’s semaglutide, a GLP-1 receptor agonist, and a fixed-dose combination of Gilead’s investigational FXR agonist cilofexor and investigational ACC inhibitor firsocostat, alone and in combination in people with compensated cirrhosis (F4) due to NASH.

The development of semaglutide in NASH is still on track and in Phase III. Based on earlier trial results, the firsocostat–cilofexor combination has also achieved statistically significant improvements in other measures of NASH, including noninvasive tests for liver enzyme levels and scarring. These results offer novel insights into the multiple mechanisms that drive NASH and demonstrate the potential of combination approaches for patients in significant need of a treatment option for this condition to elicit improvements in liver fat content, liver biochemistry, and certain noninvasive tests for fibrosis, all of which have been associated with meaningful histologic improvement in NASH. The drug is scheduled to be introduced to the US market in 2029 for NASH.

Lanifibranor/IVA337: Inventiva Pharma

Phase III

Lanifibranor is a next-generation panPPAR agonist for the safe and effective treatment of fibrotic diseases with better compliance and is the only pan-PPAR agonist in clinical development. It has been recognized as a blockbuster for NASH, a fatty liver disease, after becoming the first drug in a study that achieved two regulatory goals. Lanifibranor (IVA337) has given positive results on all NASH-related liver lesions. Lanifibranor received Fast Track and Breakthrough Therapy designations from the FDA for the treatment of NASH in September 2019 and October 2020, respectively. Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with NASH. The drug is anticipated to debut in the United States in 2026.

In 2017, Inventiva raised USD 51 million through an IPO in Paris, France. This offering gives the French biotech, which lists AbbVie and Boehringer Ingelheim among its partners, the cash to take its lead candidate through Phase IIb trials in NASH and systemic sclerosis.

In 2021, Inventiva collaborated with a member of the faculty of medicine of Angers University, who is a renowned scientist in the area of noninvasive diagnosis of liver lesions in chronic liver diseases, to treat noninvasive biomarkers to identify patients responding to lanifibranor with regards to NASH resolution and fibrosis improvement. In May 2022, Inventiva entered into a finance contract with the European Investment Bank for up to EUR 50 million, or Finance Contract, to support the preclinical and clinical pipeline, including funding a portion of the Phase III clinical trial of lanifibranor in patients with non-alcoholic steatohepatitis.

In April 2021, the company agreed with Pharmaceutical Research Associates Groupe B.V., as CRO, in connection with the NATiV3 clinical trial in NASH, with a retroactive effect in January 2021. The contract aims to support the regulatory approval of the product in adult patients in Europe and the United States. On February 1, 2022, the company amended its April 2021 agreement with PRA related to the NATiV3 clinical trial to include a bonus and malus mechanism. In September 2022, the company entered into an exclusive license and collaboration agreement with Chia Tai Tianqing Pharmaceutical Group, Co., LTD to develop and commercialize lanifibranor in Mainland China, Hong Kong Special Administrative Region, Macau Special Administrative Region, and Taiwan.

Discover which therapies are expected to grab major nonalcoholic steatohepatitis market share @ NASH Market Report

MSDC-0602K: Cirius Therapeutics

Phase III

MSDC-0602K is a second-generation insulin sensitizer designed to reduce the side effects of first-generation insulin sensitizers like edema, bone fractures, and hypoglycemia. It is hypothesized that insulin sensitization can improve non-alcoholic steatohepatitis. In the current study of patients with non-alcoholic steatohepatitis, MSDC-0602K did not demonstrate significant effects on liver histology with the biopsy techniques used. However, useful information was gained for the design of future studies, and MSDC-0602K significantly decreased fasting glucose, insulin, glycated hemoglobin, and markers of liver injury without dose-limiting side effects. Hence, MSDC-0602K can potentially become an effective treatment option for NASH patients. The drug is currently being evaluated by the company in phase III stage and it is expected to launch in 2026 in the US.

Vonafexor (EYP001): Enyo Pharma

Phase II

Vonafexor (EYP001), developed by Enyo Pharma is an orally bioavailable synthetic non-steroidal, non-bile acid FXR agonist small molecule also developed in NASH. Differentiated from other FXR agonists with its beneficial effect on kidney function (eGFR), inflammation, and fibrosis in liver and visceral fat (Phase IIa LIVIFY study in patients with NASH) and kidney diseases CKD and Alport syndrome (preclinical studies), Vonafexor has shown promising results in the NASH treatment landscape. This shows the potential of Vonafexor resulting in rapid improvement in liver function and liver fat in NASH patients. In addition to its significant impact on improving renal function, patients treated with Vonafexor are at a greater benefit to NASH patients who are often affected by comorbidities such as diabetes that significantly impact renal function.

ENYO Pharma has signed a collaboration agreement with Novadiscovery, which consists of accelerating and de-risking the clinical development of EYP001. In May 2015, POXEL SA, and ENYO Pharma SAS, announced the signing of a license agreement under which ENYO will gain access to Poxel’s FXR (farnesoid X receptor) agonist compounds for infection-related indications with Poxel retaining rights regarding therapeutic indications centered on its core expertise. No financial terms of the agreement have been disclosed.

In June 2018, ENYO Pharma completed a EUR 40 million Series B round of financing from US and European investors. This new funding enables the company to finance the two first Phase II clinical trials of its EYP001 asset in chronic HBV and NASH. In November 2021, ENYO Pharma announced that two abstracts on Vonafexor were accepted, one as an oral presentation and one as a poster, during the Liver Meeting 2021, organized by the American Association for the Study of Liver Diseases (AASLD) on November 12–15, 2021.

Supported by 9 completed clinical studies: 6 Phases I and 3 Phases IIa; the drug is currently in Phase II for CKD in patients with NASH and it is expected to launch in 2027 in the US.

HPG1860: Hepagene (Shanghai) Co., Ltd.

Phase II

Hepagene’s product pipeline includes HPG1860 for the treatment of NASH, PBC, and others. HPG1860 is a non-bile acid, potent, selective, and full FXR agonist administered orally. The drug was tolerated well in the ongoing Phase II RISE study. In the study, HPG1860 had a notable impact on liver fat content while also demonstrating satisfactory safety.  The industry has received a lot of hope from the recent data released by Intercept and Madrigal, but there is still much room for improvement. The RISE study’s findings will help HPG1860 advance clinically and support further research as the cornerstone of NASH combo therapy.

Hepagene plans to submit an abstract with detailed data from the RISE Study to an upcoming scientific conference. Based on the positive results of the Phase IIa trial, Hepagene continues with the current clinical development plan, including a combination trial of HPG1860 with HPG7233, a thyroid hormone receptor beta agonist (THR-β) developed in-house to treat NASH. The drug is expected to launch in 2027 in the US.

In April 2021, Yatra Medical Technology Co., Ltd. announced the completion of the B1 fundraising round of USD 40 million. This financing round was led by Loyal Valley Capital, existing shareholder Apricot Capital continued to participate in this investment round, and Oceanpine Capital followed suit. The funds raised in this round were mainly used for the Phase II clinical research of the farnesoid X receptor FXR agonist HPG1860 and the preclinical and clinical advancement of the company’s NASH/HBV/Liver Cancer pipeline.

On July 21, Yachuang Pharmaceutical signed a strategic cooperation agreement with Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. to conduct cooperative research on targeted combination therapy for nonalcoholic steatohepatitis (NASH). According to the agreement, the two parties will discuss the combined drug regimen of a series of pipeline products under research, including the farnesoid X receptor (FXR) agonist HPG1860 and the oral glucagon-like peptide 1 receptor (GLP-1R) agonist TPP-273 to evaluate.

Learn more about the pipeline drugs for nonalcoholic steatohepatitis @ Drugs for NASH Treatment

VK2809: Viking Therapeutics

Phase II

VK2809 is an investigational medication developed by Viking Therapeutics. It is a selective thyroid hormone receptor beta (THR-β) agonist that is being studied for the treatment of various metabolic and liver disorders. Viking Therapeutics obtained exclusive worldwide rights to VK2809, VK0214, VK5211, and other assets under an exclusive license agreement with Ligand Pharmaceuticals Incorporated, or Ligand. The terms of this license agreement are detailed in the Master License Agreement with Ligand, which the company entered on May 2014, as amended.

In November 2019, the company initiated the VOYAGE study, a Phase IIb clinical trial of VK2809 in patients with biopsy-confirmed NASH and announced the completion of patient enrollment in the VOYAGE study in January 2023, and announced positive top-line results in May 2023. The drug is expected to launch in 2028 in the US.

The consistency and durability of efficacy reported with VK2809 in the trial regardless of therapeutic dose, baseline patient characteristics, or underlying NASH risk factors is encouraging. Particularly noteworthy is that VK2809-treated patients with NASH risk factors, including elevated baseline ALT, obesity, and hypertension, experienced reductions in liver fat that were significantly greater than observed among patients receiving placebo; these latest results strongly support the ongoing evaluation of VK2809 as a potentially important treatment for NASH.

BIO89-100 (Pegozafermin): 89bio, Inc.

Phase II

Pegozafermin is a long-acting analog of glycopegylated FGF21. The half-life of native FGF21 is only half an hour. Proprietary glycopegylation technology to extend the half-life and activity of the native protein has therapeutic potential and clinical benefits to treat NASH, which is evident from the drug’s efficacy and safety results. The drug has positive topline data from a Phase IIb trial, which implies it has the potential to be used as a compelling treatment option for NASH. 

In April 2018, 89bio entered an asset transfer and license agreement with Teva Pharmaceutical Industries Ltd., where 89bio acquired certain patents, intellectual property, and other assets relating to Teva’s glycoPEGylated FGF21 program. Under this agreement, Teva also granted a perpetual, non-exclusive (but exclusive as to pegozafermin), non-transferable, worldwide license to patents and know-how related to glycoPEGylation technology for use in the research, development, manufacture, and commercialization of the compound pegozafermin and products containing pegozafermin. Under the FGF21 agreement, the company must use commercially reasonable efforts to develop and commercialize pegozafermin in the US and five major European countries. 89bio has the right to sublicense all rights licensed to them by Teva under the FGF21 Agreement. Under the FGF21 agreement and the FASN agreement (as defined and described below), 89bio paid Teva a nonrefundable upfront payment of USD 6.0 million. In addition, under the FGF21 agreement, they must make certain payments to Teva totaling USD 2.5 million for the achievement of certain clinical development milestones and additional payments totaling up to USD 65.0 million upon achievement of certain commercial milestones

In March 2023, 89bio, Inc. announced positive topline data from the Phase IIb ENLIVEN trial evaluating treatment with pegozafermin in patients with NASH. The drug is expected to enter the US market in 2027.

Efruxifermin: Akero Therapeutics, Inc

Phase II

Efruxifermin (EFX), a lead product of Akero Therapeutics, Inc. is a differentiated Fc-FGF21 fusion protein that has been engineered to mimic the balanced biological activity profile of native FGF21. EFX is currently being evaluated in two Phase IIb clinical trials in patients with biopsy-confirmed NASH: the HARMONY study in pre-cirrhotic patients with F2–F3 fibrosis and the SYMMETRY study in cirrhotic patients with compensated F4 fibrosis. Results of the main study in patients with compensated cirrhosis due to NASH (F4) are expected in the fourth quarter of 2023. 

The European Medicines Agency (EMA) designated efruxifermin as a Priority Medicine (PRIME) in October 2020. One year later, the FDA has given the drug Fast Track designation. In December 2022, efruxifermin received a Breakthrough Therapy Designation from the FDA for the treatment of NASH.

Efruxifermin is the only drug currently being evaluated for NASH pre-cirrhotic and cirrhotic patients; EFX can mimic the actions of native FGF21. As a result, if approved, this drug has the potential to be a highly differentiated, best-in-class FGF21 analog and a promising monotherapy to treat NASH. NASH is a complicated disease, and the best treatment would involve intervening at each stage of its pathogenesis. EFX can potentially address all stages of NASH pathogenesis in a single treatment, including reversing fibrosis, resolving steatohepatitis, and assisting in restoring healthy metabolism throughout the body. We also believe that EFX could be used with other therapies to achieve a greater effect in specific subpopulations. The drug is expected to launch in 2027 in the US market.

In June 2018, the company entered into a license agreement (the “Amgen Agreement”) with Amgen under which the company was granted an exclusive license to certain patents and intellectual property related to a long-acting FGF21 analog to commercially develop, manufacture, use, and distribute FGF21 as a treatment for NASH and other serious metabolic diseases. The Amgen Agreement provides the company with exclusive global rights to the licensed products and the right to grant sublicenses that cover EFX to third parties. The company also have an agreement with Vetter Pharma International GmbH, or Vetter, to manufacture EFX drug product for clinical development and plan to enter into a future agreement for commercial supply at an appropriate time. In March 2020, Akero revealed that efruxifermin is licensed from Amgen, which had beaten the placebo to reduce liver fat in NASH patients.

The other promising assests in the NASH pipeline include Denifanstat (formerly TVB-2640) (Sagimet Biosciences Inc.), Saroglitazar Magnesium (Zydus Therapeutics Inc.), Leronlimab (PRO 140) (CytoDyn, Inc.|Amarex Clinical Research), Icosabutate (NorthSea Therapeutics B.V.), Aldafermin (NGM282) (NGM Biopharmaceuticals, Inc), PXL065 (Poxel SA), LPCN 1144 (Lipocine Inc.), HTD1801 (HighTide Biopharma Pty Ltd), Rencofilstat (Hepion Pharmaceuticals, Inc.), and Belapectin (Cirrhosis) (Galectin Therapeutics Inc.).

For further information on the most promising NASH drugs, reach out @ NASH Medication Pipeline

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