Late-Stage MASH Candidates Poised to Reshape $16 Billion Market

The pharmaceutical industry is witnessing a surge in the development of novel treatments for metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH). With an estimated 22 million Americans affected by MASH and a market projected to reach $16 billion by 2033, several companies are racing to bring innovative therapies to patients.

Fibroblast Growth Factor 21 Analogs Lead the Pack

Among the most promising candidates are fibroblast growth factor 21 (FGF21) analogs, which have shown significant potential in reducing liver fibrosis. 89bio's pegozafermin and Akero Therapeutics' efruxifermin are currently in Phase III trials, with both demonstrating impressive results in earlier studies.

Pegozafermin has shown at least one-stage fibrosis improvement without worsening of MASH in Phase IIb trials, with MASH resolution rates of 26% and 23% at different dosages. Rohan Palekar, CEO of 89bio, highlighted a peer-reviewed publication ranking pegozafermin as the most efficacious drug for fibrosis improvement and MASH resolution among all approved or investigational MASH drugs.

Akero's efruxifermin, despite initial setbacks, demonstrated significant fibrosis improvement in 96-week data. Kitty Yale, Chief Development Officer at Akero, emphasized efruxifermin's unique approach, stating, "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."

GLP-1 Agonists Enter the MASH Arena

Major pharmaceutical companies are also exploring the potential of GLP-1 agonists in treating MASH. Boehringer Ingelheim's survodutide, Eli Lilly's tirzepatide, and Novo Nordisk's semaglutide are all in various stages of clinical development for MASH.

Edward Nash, senior biotechnology analyst at Canaccord Genuity, suggests that semaglutide could potentially receive FDA approval for MASH by late 2025 or early 2026. However, Nash cautions that while GLP-1s have shown the ability to reduce liver fat, their impact on fibrosis reduction remains uncertain. This limitation may lead to the exploration of combination therapies, potentially pairing GLP-1 drugs with other MASH treatments.

Emerging Approaches and Market Dynamics

Boston Pharmaceuticals is developing efimosfermin alfa, a longer-acting FGF21 analog exploring a once-monthly dosing regimen. The company plans to advance the drug into Phase III trials in the fourth quarter of 2025, with CEO Sophie Kornowski indicating plans to assess its combination with incretin treatments like GLP-1s.

Viking Therapeutics is taking a similar approach to Madrigal Pharmaceuticals' approved MASH treatment, Rezdiffra, with its thyroid hormone receptor agonist VK2809. The drug has shown promising results in Phase IIb trials, with up to 75% of patients achieving MASH resolution without fibrosis worsening.

Despite the influx of new candidates, analysts believe Madrigal's Rezdiffra will maintain a strong market position due to its first-mover advantage and established safety profile. The drug generated $180 million in full-year 2024 sales and is expected to reach blockbuster status in the coming years.

As the MASH treatment landscape evolves, the pharmaceutical industry anticipates significant growth opportunities, with multiple companies vying to capture a share of this expanding market.