After last year’s ‘stampede’ for FGF21 assets, the focus for the metabolic dysfunction-associated steatohepatitis space has shifted toward differentiated approaches, such as THR-β agonists and combination treatments, that seek to mirror the commercial success of Madrigal’s Rezdiffra.
Before Madrigal’s Rezdiffra, the quest for a cure for metabolic dysfunction-associated steatohepatitis was a veritable graveyard for drug developers. However, the 2024 approval of that first drug for the inflammatory liver disease demonstrated to the pharma industry that the feat was possible. Not only that, but Madrigal proved it could be lucrative.
In November 2025, the company announced in its third-quarter financial update that Rezdiffra had generated revenues of $287 million, just six quarters after its launch. Altogether, the product has amassed $817 million in revenue for its maker. This commercial success has not gone unnoticed, with three Big Pharma acquisitions in the MASH space in 2025, all worth billions of dollars.
GSK began the rush in May by acquiring the investigational FGF21 analog efimosfermin alfa from Boston Pharmaceuticals for $1.2 billion upfront. Then, in September, Roche snapped up 89bio and another FGF21 analog pegozafermin for around $3.5 billion. Novo Nordisk followed weeks later with a $5.2 billion deal for Akero Therapeutics.
The spate of acquisitions—all focused on FGF21 analogs—was centered on the success of Akero Therapeutics’ efruxifermin, which, in January 2025, showed positive long-term data in a mid-stage trial.
“I think that really set off the stampede because there were very few FGF21 assets in development,” Edward Nash, managing director at Canaccord Genuity, told BioSpace. “This caused a big pharma reaction of, ‘Wait a minute, we need one of those too because we have a metabolic franchise and we need to be able to compete, especially given the data seen to date in the FGF21 space.’”
This, alongside the approval of Novo Nordisk’s GLP-1 weight-loss blockbuster Wegovy for MASH, has led to the market opening up, and now, more companies want in, Nash said.
All of this activity means the overall MASH landscape has changed significantly in the past year. With the key FGF21 developers off the market, there is an increased focus on the other assets in the field’s late-stage pipeline. Here are four candidates, each with differentiated mechanisms of action, that Big Pharma companies could have in their sights in 2026.
Inventiva Homes In On Potential Next Oral MASH Drug
Inventiva’s upcoming Phase III readout for pan-PPAR agonist lanifibranor is “the biggest event in the MASH space” this year, according to Nash.
“It’s been a long trial, and it’s been long-awaited by the Street,” he said. “Depending on the data, [Inventiva] could definitely become another takeover candidate.”
The French biotech is now solely focused on lanifibranor after halving its workforce and stopping all preclinical research not related to the drug to help fund its development in February 2025.
This singular focus will help push the drug through its Phase III trial, with Inventiva poised to publish topline results from the NATiV3 trial in the second half of 2026. With these data expected, “lanifibranor could potentially be the next oral therapy approved for the treatment of patients with MASH,” CEO Frederic Cren said in a statement in April 2025.
Lanifibranor is an oral small molecule that activates three peroxisome proliferator-activated receptor (PPAR) isoforms. Through the activation of these isoforms, Inventiva aims to address the key drivers of the disease, including inducing anti-fibrotic, anti-inflammatory and beneficial metabolic changes.
In the NATIVE Phase IIb trial, reported in June 2020, lanifibranor achieved statistically significant MASH resolution and fibrosis improvement, with 42% of patients who received a 1200 mg dose seeing fibrosis improvement vs. 24% of placebo comparators after 24 weeks.
The path to this year’s Phase III readout has not been straightforward for Inventiva. In February 2024, the company voluntarily suspended screening and enrollment of patients in NATiV3 after a patient exhibited severely elevated aminotransferase levels.
Now, Inventiva expects the results from NATiV3, if positive, to form the basis for a submission for regulatory approval.
Viking Still Up For Grabs
Viking Therapeutics has long attracted significant interest from Big Pharma. With pipeline assets that target both obesity and MASH, analysts have marked the biotech as one likely to draw suitors.
For MASH, the company is developing VK2809, an oral thyroid hormone receptor-beta (THR-β) agonist. In the Phase IIb VOYAGE trial, VK2809 demonstrated a 37%-55% mean reduction in liver fat, with up to 75% of patients reaching MASH resolution without fibrosis worsening, according to data released in November 2024.
In addition to these outcomes, the drug also demonstrated lipid-lowering effects and minimal side effects, Brian Lian, CEO of Viking, told BioSpace in an email. The overall body of evidence for VK2809 makes it “highly competitive” against both marketed products and drug candidates for MASH, he added.
While Lian has previously stated that Viking would be open to partnering on the asset and confirmed that the company is still exploring partnering opportunities—he previously said that having a partner is not mandatory in order to bring the product to the market.
Altimmune Open to Partnering Pemvidutide But Could Go It Alone
Altimmune’s pemvidutide stands apart from others in the MASH pipeline due to its ability to preserve lean muscle mass, as well as ensuring MASH resolution and weight loss, a company spokesperson told BioSpace in an email.
Pemvidutide is a weekly injectable GLP-1/glucagon dual receptor agonist that last month received the FDA’s Breakthrough Therapy Designation for MASH. This follows the November release of Phase IIb data from Altimmune’s IMPACT study, which showed that 52% of patients achieved MASH resolution without worsening of fibrosis, as well as improvements to liver fat content and weight loss.
Altimmune is in a similar position to Viking, as both companies have the data to progress their drugs into Phase III, but may not begin those trials until they can find a partner, Nash said.
“These two companies are all in on obesity, and that treatment area is already a big enough nut to crack,” he added. “To try to do that and run a MASH trial at the same time, I think you’re going to get a lot more bang for your buck if your molecule is differentiated in obesity.”
The Altimmune spokesperson countered this, however, saying that independently bringing the asset forward in MASH is a “legitimate path forward.” However, they also noted that Altimmune remains open to any opportunity “that adds value, including partnerships.”
Sagimet Looks to Combo FASN Inhibitor For Optimum Effect
Like pemvidutide, Sagimet Biosciences’ denifanstat, an oral, once-daily fatty acid synthase (FASN) inhibitor that blocks the production of new fat in the liver, holds FDA Breakthrough Therapy Designation in MASH. Unlike Altimmune, however, Sagimet is not considering pursuing a Phase III trial alone, according to Nash. Instead, the California-based company is looking to cement its drug as a validated part of a combination therapy.
In line with this, Sagimet released data in December from a Phase I trial that featured denifanstat paired with Rezdiffra, the current market leader. The trial showed that the combination was well-tolerated, and Sagimet plans to advance denifanstat into Phase II efficacy trials for MASH patients with F4 fibrosis. The combined treatment could boost fibrosis reduction more than Rezdiffra alone, Nash said.
This type of combination approach is likely to be the future of MASH treatments because the disease is multifactorial, he added, with the main two targets being liver fat and fibrosis.
So far, the marketed drugs— Rezdiffra and Wegovy—and the investigational pipeline have not proven outstanding at hitting both of these targets, making a combination treatment approach logical, Nash said.
It seems the same could be true for the companies themselves, with partnering and M&A the likeliest outcome for the smaller players in the MASH landscape.
“It’s hard to be successful as a standalone company,” Nash said. “There’s usually only one company when that happens, like Madrigal. I think we’re going to have one, maybe two biotechs, that can do it—after that, it’s going to be Big Pharma taking them in and developing them.”
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