Efruxifermin

iStock, Elena Merkulova Akero Therapeutics, 89bio, Boston Pharmaceuticals and more are working to bring novel treatment options for metabolic dysfunction-associated steatohepatitis to a market that could reach $16 billion by 2033. It’s been a little more than a year since the FDA approved Madrigal Pharmaceuticals’ Rezdiffra as the first treatment for the liver disease metabolic dysfunction-associated steatohepatitis. After earning $180 million in full-year 2024 sales , Madrigal expects Rezdiffra to reach blockbuster status in the coming years. With an estimated 22 million Americans living with metabolic dysfunction-associated steatohepatitis (MASH)—previously known as nonalcoholic steatohepatitis (NASH)—there is a growing pipeline of potential therapies, and several companies are expecting Phase III readouts in 2025. Rather than relying on one strategy, the leading candidates are approaching the disease from different angles. This could allow more assets to carve out a share of a market that is expected to be worth $16 billion by 2033 . Rezdiffra’s early success, along with clinical research suggesting that GLP-1 drugs could also have therapeutic potential in MASH, has analysts optimistic about the growth potential of the space. “That’s why Rezdiffra has been so heavily watched and why there are so many drugs in development for MASH,” Edward Nash, senior biotechnology analyst at Canaccord Genuity, told BioSpace . “It’s thought of as having the potential to be the next type 2 diabetes for the industry. It’s that big of a metabolic disease, and it offers multi-billion dollar opportunities for many different treatment mechanisms.” Here, BioSpace looks at five candidates that could soon emerge on the market. 89bio’s Pegozafermin Fibroblast growth factor 21 analog Currently undergoing Phase III trials , 89bio’s pegozafermin is part of a class of treatments for MASH that mimics the activity of fibroblast growth factor 21 (FGF21), a hormone produced by the liver that acts as a metabolic regulator. According to Nash, FGF21 analogs have generated the most attention because they’ve shown a “really strong ability to reduce liver fibrosis,” which is damage to the liver caused by the chronic inflammation associated with MASH. So far, pegozafermin is no exception. Phase IIb trial results showed the candidate managed at least one-stage fibrosis improvement at two different dosage levels (30 mg weekly and 44 mg every-other week) without worsening of MASH. In addition, MASH resolution without worsening of fibrosis was managed at 26% and 23%, dependent on the dosage. Rohan Palekar, CEO of 89bio, pointed to a recent peer-reviewed publication where pegozafermin was ranked as the most efficacious drug for fibrosis improvement and MASH resolution among all approved or investigational MASH drugs. “A key distinction is that pegozafermin has also shown a favorable safety and tolerability profile, with few gastrointestinal side effects and no clinically significant effect on bone density,” Palekar told BioSpace in an email. Akero Therapeutics’ Efruxifermin Fibroblast growth factor 21 analog Akero finds itself in a similar position to 89bio, with a FGF21 analog in Phase III trials. However, the biotech’s path to this point, at least from a shareholder perspective, has been more tumultuous. Akero’s stock price sunk in October 2023 after efruxifermin missed its primary endpoint of 36-week fibrosis improvement in a Phase IIb trial. The drug’s prospects were saved five months later when the biotech was able to show in 96-week data that fibrosis was significantly improved in patients with MASH. “Unlike other MASH drugs that target [a] specific pathway, efruxifermin delivers sustained FGF21 signaling to both liver and adipose tissue, aiming to correct metabolic imbalances that drive disease progression,” Kitty Yale, chief development officer at Akero, told BioSpace over email. “While some obesity drugs aid weight loss, they may not directly target the liver, limiting their impact on fibrosis.” The biotech has a Phase III program comprising three ongoing clinical trials aimed at supporting future regulatory applications of efruxifermin for patients with compensated cirrhosis due to MASH and with pre-cirrhotic MASH, Yale added. Boehringer Ingelheim, Eli Lilly, Novo Nordisk: Survodutide, Tirzepatide, Semaglutide GLP-1 agonists A fierce competition is underway between weight loss rivals, as GLP-1 drug developers attempt to differentiate their treatments . One strategic angle has been to target MASH as an additional indication to support the drugs’ widespread use. According to Nash, an approval in MASH would boost GLP-1s’ appeal for physicians because it would allow them to address three metabolic diseases—type 2 diabetes, obesity and MASH—with the same treatment. Boehringer Ingelheim, Eli Lilly and Novo Nordisk have all adopted this approach. Boehringer and Novo Nordisk have progressed survodutide and semaglutide , respectively, through to Phase III trials, and Lilly posted positive Phase II trial results for tirzepatide in June 2024. Of the GLP-1s currently being studied for MASH, Nash suggested that semaglutide is the closest to potential FDA approval, projecting that an approval could come by the end of 2025 or in the early part of 2026. While clinical trials have indicated that GLP-1s can reduce fat in the liver, that does not necessarily indicate that fibrosis will also be reduced, Nash cautioned. Due to this limitation, GLP-1 drug developers will likely explore combination therapies, which could see other approaches to MASH combined with GLP-1 medicines, he added. Both Palekar and Yale said they are exploring using their MASH candidates in conjunction with GLP-1s. Boston Pharmaceuticals’ Efimosfermin Alfa Fibroblast growth factor 21 analog Boston Pharmaceuticals’ FGF21 analog is a little bit different. A fusion protein based on human IgG and FGF21, efimosfermin alfa is longer-acting than other late-stage rivals in the MASH pipeline, with Boston exploring a once-monthly regimen for the drug. In November 2024, the potential treatment elicited a one-stage improvement in fibrosis without worsening of MASH in a Phase II trial . The biotech plans to advance efimosfermin into Phase III trials in the fourth quarter of this year, according to CEO Sophie Kornowski. Similar to other companies working in the space, the next stage of trials will assess how efimosfermin pairs with incretin treatments for diabetes, such as GLP-1s, Kornowski told BioSpace via email. Nash likened Boston’s dosing to approaches in immunology and inflammation, where when rival drugs’ clinical outcomes are similar and the longer dosing schedule drugs are preferred. Margaret Koziel, chief medical officer at Boston, told BioSpace by email that efimosfermin’s increased half-life is enabled by “several point mutations and an additional disulfide bond that prevents proteolytic degradation.” Viking Therapeutics’ VK2809 Thyroid hormone receptor agonist Adopting a similar approach to Madrigal, Viking has a thyroid hormone receptor agonist as its lead candidate for MASH. The biotech posted positive Phase IIb data in November 2024 showing that up to 75% of patients treated with VK2809 reached MASH resolution without fibrosis worsening. A further 57% showed at least a one-stage improvement in fibrosis without deterioration of MASH. Like Rezdiffra, VK2809 is a small molecule, oral treatment. In Phase II studies, Viking carried out both a daily and an every-other-day dosing schedule. In full-year results released in February 2025 , Viking stated that it considered its drug candidate “best-in-class” but only noted that it is “currently evaluating potential next steps” for VK2809. Should the development of VK2809 prove successful, the biotech could explore trialing the treatment alongside its own GLP-1 treatment candidate, VK2735, providing Viking with an in-house combination therapy. Despite this healthy roster of candidates, Nash said it is unlikely that any of them will be able to fully displace Rezdiffra. “Given their lead over the competitive landscape and being on the market first, Madrigal is going to have entrenched itself by the time competitors arrive,” he concluded. “Plus, it’s a safe drug—so, it’s a nice, solid foundational drug to have on the market.”

Eli Lilly is buying Organovo’s farnesoid X receptor (FXR) agonist program, which includes a drug in Phase 2 development for ulcerative colitis and metabolic dysfunction-associated steatohepatitis (MASH), the biotech said Tuesday . The drugmaker will pay $9 million upfront plus $1 million in 15 months and up to $50 million in milestones, according to an SEC filing . Lilly is obtaining all worldwide rights to the program. Organovo’s share price $ONVO nearly tripled in early trading on Tuesday. The deal is remarkable because Intercept Pharmaceuticals’ attempts to pursue this mechanism in MASH ended in grave disappointment. The FDA rejected the company’s treatment, called Ocaliva, for the fatty liver disease — which used to be called NASH — in 2020 . A subsequent Phase 3 trial failed too . Since then, FXR agonism has been superseded as a MASH approach by other mechanisms like thyroid hormone receptor beta agonism (used by Madrigal’s approved Rezdiffra and Viking Therapeutics’ experimental VK2809, among others) and FGF21 agonism (used by assets which include Akero’s efruxifermin and 89bio’s pegozafermin). That said, it’s not clear that Lilly intends to pursue Organovo’s asset, called FXR314, in MASH. The only indication mentioned in Organovo’s statement is inflammatory bowel disease, and Lilly has not commented. However, Organovo has trialed the drug in the disorder. The company presented Phase 2 data in November that showed statistically significant reductions versus placebo in liver fat, a commonly used biomarker in early MASH trials. According to its website , it was actively seeking a partner for this indication.