NASH is a severe form of non-alcoholic fatty liver disease (NAFLD), where fat builds up on the liver, potentially leading to liver damage or cirrhosis. With no U.S. Food and Drug Administration (FDA)-approved treatments for the disease, many NASH companies are currently attempting to bring their candidates toward approval. In this article, we take a look at five of the companies that are edging closer and closer to the finish line.
Over the years, many biotech and pharma companies have tried to pursue an effective treatment for NASH, with very little success. Even Intercept, which for a long time was a frontrunner in the race to get its NASH candidate approved, failed to achieve its goal, after receiving a second rejection from the FDA for Ocaliva in June 2023.
However, the multitude of NASH failures has not put off companies from still trying to develop an effective treatment. In fact, many NASH companies currently have their candidates in late-stage trials, and it is only a matter of time before one of them succeeds in bringing their treatment to market.
With this in mind, here are five NASH companies that could potentially have their treatments approved in the coming years.
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Galectin Therapeutics is focused on creating new therapies for patients with chronic liver disease, as well as skin diseases and cancer. The company’s drug candidates are based on its carbohydrate technology, and work by targeting galectin proteins, which are key mediators of biologic and pathologic function.
The company is developing a candidate called belapectin for the treatment of NASH cirrhosis and NASH fibrosis. Belapectin is a complex carbohydrate drug that targets galectin-3, which is a critical protein in the pathogenesis of NASH and fibrosis, playing a major role in diseases that involve scarring of organs, including fibrotic disorders of the liver, lung, kidney, heart, and vascular system. Therefore, belapectin is designed to bind to galectin-3 in order to disrupt its function.
Galectin is currently conducting a phase 2b/3 study of belapectin in patients with NASH cirrhosis called NAVIGATE. For the trial, patients have been recruited from 14 different countries across five continents. The main efficacy objective of the study is the primary prevention of esophageal varices, a potentially life-threatening complication of liver cirrhosis brought about by portal hypertension, which itself is the consequence of the unrelenting inflammatory and fibrotic process occurring in the liver.
The company announced at the beginning of 2023 that it had completed enrollment in the NAVIGATE study. The treatment period is 18 months, meaning the results of the interim analysis are expected in the fourth quarter of 2024.
Based in Israel, Galmed Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing Aramchol – its lead drug candidate – for liver and fibro-inflammatory diseases. To date, the company has focused almost exclusively on developing Aramchol for the treatment of NASH.
Aramchol is a first-in-class, novel synthetic small molecule that works by targeting stearoyl-CoA desaturase 1 (SCD1), the rate-limiting step in the synthesis of monounsaturated fatty acids. It is currently being investigated in a phase 3 multinational clinical trial called ARMOR for adults with NASH and liver fibrosis. The study is currently underway in 17 countries across five continents, involving 2,000 patients.
Galmed is also exploring the feasibility of developing Aramchol for other fibro-inflammatory indications outside of liver disease, and is collaborating with the Hebrew University in developing another drug candidate called Amilo-5MER, which is a 5 amino acid synthetic peptide currently intended as an oral treatment for mild to moderate ulcerative colitis.
Inventiva Pharma is working on developing novel and differentiated oral small molecule therapies for patients suffering from diseases with significant unmet clinical need, with a particular focus on fibrosis, lysosomal storage disorders, and oncology. Its lead candidate is called lanifibranor, and is being developed to treat NASH. It is currently in phase 3 of clinical development.
Lanifibranor acts to induce anti-fibrotic, anti-inflammatory, and beneficial metabolic changes in the body by activating each of the three PPAR isoforms, known as PPARα, PPARδ, and PPARɣ. PPARs are ligand-activated transcription factors belonging to the nuclear hormone receptor family that regulate the expression of genes. They play essential roles in the regulation of cellular differentiation, development, and tumorigenesis.
In August 2023, Inventiva raised approximately €35.7 million ($38.9 million) in funding from new and existing investors. The NASH company said it intended to use 95% of the net proceeds from this financing for the phase 3 trial of lanifibranor, as well as the remaining 5% for its other clinical and preclinical programs and corporate purposes.
Madrigal Pharmaceuticals is fully concentrating its efforts on NASH, with its lead clinical candidate resmetirom currently being studied in phase 3 trials for the treatment of patients with NASH with significant liver fibrosis and NASH with compensated cirrhosis.
Resmetirom is a THR-β agonist, which targets thyroid hormone receptor-β. Activation of this receptor is associated with systemic lipid lowering, increased bile acid synthesis, and fat oxidation.
Resmetirom has presented positive data in a phase 3 study known as MAESTRO-NASH. It was found to resolve liver biopsy findings in the liver disease more often than placebo. While only 10% of placebo patients achieved resolution of inflammation, ballooning, and disease activity, the rate was 26% among patients treated with an 80mg dose of resmetirom, and 30% among patients who received a 100mg dose.
Resmetirom has received an FDA breakthrough therapy designation. Following Intercept’s withdrawal from the NASH drug race, Madrigal now looks the most likely to become the first company to have its NASH treatment approved.
Based in San Francisco, 89bio is on a mission to develop and deliver innovative therapies to treat patients with liver and cardiometabolic diseases. Its lead candidate is called pegozafermin, and is an investigational glycopegylated FGF21 analog currently being evaluated for the treatment of NASH, as well as severe hypertriglyceridemia (SHTG). FGF21 is an endogenous hormone primarily secreted from the liver that acts as a master metabolic regulator with broad effects on energy expenditure and glucose and lipid metabolism.
In November, 89bio announced positive topline data from the blinded extension phase of its phase 2b ENLIVEN trial, evaluating pegozafermin in patients with NASH. At week 48, both the 30mg weekly and 44mg every-two-week dosing schedules of pegozafermin demonstrated statistically significant improvements across key markers of liver health. The benefits observed at week 48 were consistent with the results observed at week 24, indicating sustained benefits over time. The efficacy endpoints assessed included liver fat, non-invasive markers of fibrosis and inflammation, and metabolic markers.
Pegozafermin has received an FDA breakthrough therapy designation, and phase 3 studies of the drug for NASH are currently being planned out.
Looking ahead: NASH market expected to grow over the next decade
In 2022, the industry size of NASH treatment was already over $5.2 billion. And, now, the NASH treatment market is expected to grow over the next decade, with its size anticipated to reach $48.3 billion by the end of 2035. This means it would grow at a compound annual growth rate (CAGR) of 18% during this period.
Over the past few years, many companies – both small biotechs and big pharmas – have tried and failed to develop an effective NASH treatment. But with the companies listed in this article now racing to bring their candidates toward the finish line, it might not be long before we see multiple companies succeed in their quest to bring a NASH treatment to market.