7 Late-Stage MASH Candidates That Could Reshape the Market

 

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.”

https://www.biospace.com/drug-development/7-late-stage-mash-candidates-that-could-reshape-the-market

Hamas fires rockets at Israeli cities, Israel issues evacuation orders in Gaza

 Palestinian militant group Hamas said it fired a barrage of rockets at cities in Israel's south on Sunday in response to Israeli "massacres" of civilians in Gaza.

Israel's military said about 10 projectiles were fired, but most were successfully intercepted. Israel's Channel 12 reported a direct hit in the southern city of Ashkelon.

Israeli emergency services said they were treating one person for shrapnel injuries, and teams were en route to locations of fallen rockets. Smashed car windows and debris lay strewn on a city street, videos disseminated by Israeli emergency services showed.

Meanwhile, Gaza local health authorities said Israeli military strikes killed at least 39 people across the Gaza Strip on Sunday.

Shortly after the rocket firing, the Israeli military posted on X a new evacuation order, instructing residents of several districts in Deir Al-Balah city in the central Gaza Strip to leave their areas, citing earlier rocket firing.

"This is a final warning before the attack," the military warning statement said.

Later, it said it struck the rocket launcher from which projectiles were launched earlier from the Gaza Strip.

Israeli Prime Minister Benjamin Netanyahu, on a flight to Washington for a meeting with U.S. President Donald Trump, was briefed on the rocket attack by his Defense Minister, Israel Katz.

A statement issued by his office said Netanyahu instructed that a "vigorous" response be carried out and approved the continuation of intensive activity by the Israeli military against Hamas.

Israel's Channel 12 television said at least 12 lightly injured people have been treated as a result of the rocket firing from Gaza, quoting officials at the Bazilai Hospital in Ashkelon.

The first phase of a ceasefire between Israel and Hamas went into force on January 19 after 15 months of war and involved a halt to fighting, the release of some of the Israeli hostages held by Hamas, and the freeing of some Palestinian prisoners.

However, Israel said on March 19 that its forces resumed ground operations in the central and southern Gaza Strip. Both parties blamed one another for a stalemate in the ceasefire talks.

More than 50,000 Palestinians have been killed by the Israeli offensive in Gaza, Palestinian officials say.

Israel began its offensive after thousands of Hamas-led gunmen attacked communities in southern Israel on October 7, 2023, killing 1,200 people and abducting 251 as hostages, according to Israeli tallies.

https://www.yahoo.com/news/hamas-fires-rockets-israeli-cities-192050494.html

'Goldman Sachs expects significant Chinese fiscal easing to offset tariffs'

 Goldman Sachs said it expects Chinese policymakers to accelerate fiscal easing measures significantly to offset the drag on growth from higher tariffs announced by the United States last week that were higher than expected.

Goldman said in a report on Sunday that the new tariff rates announced by U.S. President Donald Trump would lower Chinese GDP growth by at least 0.7 percentage point this year.

"Prior to the tariffs, growth was tracking above our forecasts, and we were contemplating an upward revision to our 2025 GDP expectations," the report said.

Goldman pointed to a commentary in China's state-run People's Daily on Sunday that hinted at monetary policy actions and listed measures China could take.

"Based on the evolving situation, there is ample room for adjustment in monetary policy tools such as reserve requirement ratio cuts and interest rate reductions, which can be introduced at any time," the newspaper said.

The People's Daily also pointed to a possible further expansion of fiscal deficits, special bonds, and special treasury bonds. China will take "extraordinary measures" to boost domestic consumption, accelerate implementation of established policies, and introduce a batch of reserve policies, it said.

Goldman said in a separate report, also released on Sunday, that it kept its 2025 GDP growth forecast for China at 4.5% due to better-than-expected first-quarter data and increased policy easing expectations, but trimmed its earnings growth forecast for the year to 7% from 9%.

Trump introduced an additional 34% tariff on Chinese goods as part of steep levies imposed on most U.S. trade partners, bringing the total duties on China this year to 54%. China retaliated with a series of countermeasures.

The investment bank also downgraded Taiwan to underweight in its Asian market allocations, citing high exposure to U.S. exports and market sensitivity.

https://finance.yahoo.com/news/goldman-sachs-expects-further-fiscal-004855485.html

Inflation?

 

https://finviz.com/futures.ashx

Dems "Openly Defending" Hiring Illegal Immigrants After Wash. State ICE Raid

 ICE raided Mount Baker Roofing in Bellingham, Washington this week as part of an “ongoing criminal investigation into the unlawful employment of aliens without legal work authorization”, according to Jason Rantz at 770KTTH. 

The agency reported arresting 37 illegal immigrants “who had fraudulently represented their immigration status and submitted fraudulent documents and/or information to seek employment.”

Rantz this week writes to point out that Democrats are simply "openly defending businesses hiring illegal immigrants". 

ICE described its investigation as targeting “worksite violations and/or the exploitation of workers”—a goal Democrats usually support, unless it involves illegal immigrants.

The Washington State Senate Members of Color Caucus (MOCC) condemned the raid, claiming it harms business. “Businesses also face significant challenges, including labor shortages, operational disruptions, and uncertainty in their ability to provide goods and services,” they stated.

Rantz writes that Washington Democrats appear more concerned about businesses allegedly hiring illegal workers than about the violations themselves. They've even funneled millions into helping illegal immigrants avoid deportation and continue working unlawfully.

Illegal workers are often exploited, but Washington Democrats seem fine with that—as long as they can use them to posture as champions of the marginalized. Even if the arrests had involved violent criminals, their outrage would still be directed at ICE, not the lawbreakers.

Roofing isn't one of those jobs Democrats claim Americans refuse to do, so why defend illegal employment? Is it just about securing cheap labor while locals face a 4.9% unemployment rate in Bellingham?

If you're questioning their priorities, the MOCC's statement says it all—and not in a flattering way, Rantz concludes.

https://www.zerohedge.com/markets/dems-openly-defending-hiring-illegal-immigrants-after-wash-ice-raid

NY plotting another tax hike to keep feeding health care special interests

 In a tale all too typical of Albany, Gov. Kathy Hochul a year or so ago was pushing to rein in out-of-control state Medicaid spending on home health aides, only to since switch sides with an eye on her re-election run next year.

Now Medicaid outlays are set to soar at least 17% in the next budget, while the aide ranks are soaring and indeed are by far the single largest job category in all New York.

A new Empire Center analysis of US Bureau of Labor Statistics data shows that the Empire State home-health-aide workforce grew by 57,000 from 2023 to May 2024, for a total of 623,000.

That’s far above the per-capita level of other states and outnumbers New York’s No. 2. job category, retail sales, by nearly three to one.

This year, Hochul’s initial budget proposed a 17% rise in Medicaid spending (some of it buried in other categories); the Legislature will almost certainly add to that somehow, since the health-care-worker unions — above all, 1199 — are a ginormous lobbying power.

This, when state Medicaid spending has seen double-digit growth and a surge in enrollment despite a falling poverty rate.

And when New York’s overall health-care workforce grew from 1.15 million workers pre-pandemic (2019) to 1.40 million in 2024.

Hochul had hoped to rein in the home-aide ranks by centralizing hiring in her Consumer Directed Personal Assistance Program, but that’s since morphed into a mass unionization drive after an administrative maneuver that opened the door for 1199 to sign up the aides as members (even as the firm tapped to run the centralized hiring has itself been a subject of controversy).

Meanwhile, Hochul’s team also allowed New Yorkers without employer-sponsored health benefits to qualify for home-care-aide subsidies under the state Essential Plan, another big boost for 1199.

o be fair, the unions aren’t the only special interest to push ever-higher health spending: The state’s hospitals are a lobbying monster in their own right, and a host of nonprofit insurers and other intermediaries regularly spin off huge payouts to the private interests that control them in various state-approved “restructurings.”

Of course, since Medicaid is a joint state-federal program, New York’s vast outlays (and those of other ill-governed states like California and Illinois) will soon face some tough love from Washington; cuts in payments to the Empire State will hit the $10 billion range — not that anyone now negotiating the new state budget cares to plan on it.

Hochul and all the other Dems who rely on the political support that uncontrolled health spending buys will scream about Republicans’ “savagery” when the time comes, and most likely “temporarily” hike a host of New York taxes to balance the books.

Voters, consider yourselves on notice.

https://nypost.com/2025/04/06/opinion/new-york-is-plotting-another-tax-hike-to-keep-feeding-health-care-special-interests/

Exposure to antibiotics as a newborn can impair immune response to vaccines

 Immunization programs save millions of lives every year by protecting against preventable diseases. The immune response to vaccines, however, varies significantly between individuals, and the results can be suboptimal in populations at a higher risk of developing infectious diseases. Growing evidence suggests that differences in gut microbiota could be a key factor driving these variations.

A recent Australian study published in Nature found that babies treated with antibiotics within the first few weeks of their life showed weaker immune response to vaccines due to reduced levels of Bifidobacterium—a bacterial species that lives in the human gastrointestinal tract. Replenishing Bifidobacterium in the gut microbiome using probiotic supplements such as Infloran showed promising results in restoring the immune response.

The researchers followed 191 healthy, vaginally born infants from their birth to 15 months: 86% of the participants received the hepatitis B vaccine at birth, and, by six weeks of age, began their routine childhood vaccinations, according to the Australian National Immunization Program schedule.

The infants were grouped based on their exposure to antibiotics: no direct or maternal exposure, exposed to maternal antibiotics and received at least 48 hours of antibiotic treatment during neonatal care.

To monitor changes in gut microbiome and vaccine-related immune responses over time, stool samples were collected at seven days and six weeks of age, while blood samples were taken at multiple points between six weeks and 15 months. To prevent bias during sample collection and analysis, the researchers collecting the samples weren't aware of which infants belonged to which exposure group.

Vaccine-specific antibody responses are frequently impaired in infants directly exposed to antibiotics in the neonatal period. Credit: Nature (2025). DOI: 10.1038/s41586-025-08796-4

The investigation revealed that children who were directly exposed to neonatal antibiotics, not the ones exposed to maternal antibiotics, produced much lower levels of antibodies against multiple polysaccharides included in the 13-valent pneumococcal conjugate vaccine or PCV13 vaccine.

Streptococcus pneumoniae, a bacteria known for causing serious diseases like pneumonia, blood infections, and meningitis, is surrounded by a capsule made up of polysaccharides, or sugar molecules that help the bacteria evade attacks by the body's immune system.

The PCV13 vaccine makes it easier for the immune system to attack S. pneumoniae and produce antibodies by linking the polysaccharide capsule layer to proteins. Exposure to neonatal antibiotics reduces antibody production against such polysaccharides, weakening the immune response.

Experiments on germ-free mice revealed that the lower immune response was linked to a reduced abundance of Bifidobacterium in the gut microbiome. However, giving the mice a mix of Bifidobacterium species or Infloran, a commonly used infant probiotic, helped reverse the negative effects of antibiotics and regain the immune response to PCV13.

The researchers propose that restoring a healthy Bifidobacterium-rich microbiota in antibiotic-exposed infants before their vaccination might enhance the antibody responses to vaccination, leading to better protection against infectious diseases.

More information: David Lynn, Bifidobacteria support optimal infant vaccine responses, Nature (2025). DOI: 10.1038/s41586-025-08796-4. www.nature.com/articles/s41586-025-08796-4

https://medicalxpress.com/news/2025-04-exposure-antibiotics-newborn-impair-immune.html