NASH Market Size Remains a Mystery: From 30 Million to Billions of Dollars, Industry Diverges Sharply

Researchers are confident that a liver disease called NASH (nonalcoholic steatohepatitis) affects a large number of people, but they cannot determine the exact number.

The National Institutes of Health (NIH) gives a broad estimate: the prevalence among American adults ranges from 3% to 12%, or about 10 million to 30 million people. This estimate dates back to two studies that together covered data from fewer than 400 patients. The NIH division responsible for liver disease management does not have its own statistics on the number of NASH patients.

"These numbers are closer to astrology than astronomy," said Pasha Sarraf, an analyst at SVB Leerink, in an interview with BioPharma Dive, commenting on NASH population estimates overall. "They are just made-up numbers," he said. "I don't believe any of them."

The size of the NASH population is not the only uncertainty.

Pharmaceutical companies and liver organizations have signaled that NASH drugs representa $35 billion market opportunity。

but investment banks hold more conservative views. Credit Suisse predicts the market will reach $20 billion by 2030. SVB Leerink expects around $12 billion to $14 billion in the same year. RBC Capital Markets models a forecast of $7 billion for 2026.

Given precedents in other liver disease drug markets, these estimates may still be too high.

Take hepatitis C, for example, whose market at its peakreached annual sales of about $22 billion. Although that disease affects far fewer patients than the expected NASH population, its viral nature means patients must receive drug treatment. In contrast, patients with milder NASH may benefit from lifestyle changes.

In another less common liver disease, primary biliary cholangitis (PBC), Sarraf noted that the monopoly held by Intercept Pharmaceuticals and its drug obeticholic acid (brand name Ocaliva) did not prove particularly lucrative. Ocaliva's net sales in 2018 were $178 million.

"PBC patients are very motivated," Sarraf said. "Their livers are failing, and they must be treated. It's not optional."

Meanwhile, NASH is caused by fat accumulation in the liver, leading to fibrosis over time. Patients often remain unaware for decades, and weight loss through diet and exercise can slow or even reverse liver fibrosis.

Research also shows that NASH is more complex than other liver diseases, involving many developmental pathways that are not yet well understood. This may make doctors hesitant when prescribing drugs.

"Overall, hepatologists are excited about the prospect of finding effective drugs. But I also worry that we will find drugs that work for some people but not others, and we won't be able to explain why," said Zachary Henry, a hepatologist at the University of Virginia Health System.

Competing for the same patients

NASH patients may experience severe liver damage, but not always—at least according to the limited epidemiological data available. A study published in 2015meta-analysisfound that among 411 adults with NASH or the more general fatty liver disease, 15% were in the two highest stages of the widely used five-stage fibrosis scale.

However, this group is exactly what many NASH drug companies are initially targeting, because the sickest patients are expected to be the most likely to receive prescriptions and subsequently obtain insurance coverage for drug treatment.

The four most advanced experimental NASH drugs—Intercept's obeticholic acid, Gilead's selonsertib, GenFit's elafibranor, and Allergan's cenicriviroc—have all been tested in clinical trials in patients at the middle-to-high stages of the fibrosis scale.

Only Intercept's drug achieved positive data in a Phase III trial, but even in that trial, the proportion of patients reaching the primary endpoint was less than one quarter. Depending on the obeticholic acid dose, 28% to 51% of patients experienced itching, which could be problematic because NASH is largely asymptomatic in its early stages.

Getting positive data and regulatory approval is only the first hurdle to cross. Intercept and other companies may have trouble finding patients with moderate-to-severe NASH—not because the number of patients is small, but becausediagnosing NASH itself is challengingThe best method is an invasive liver biopsy, but neither patients nor doctors are very fond of it.

Payers, cautious about liver disease and weight-loss drugs based on past experience, are also likely toset up barriers。

First-mover advantage is not significant

A smaller-than-expected market opportunity could weigh heavily on small biotech companies, whose value largely derives from potential NASH drugs. Mid- and small-cap companies such as Viking Therapeutics, Madrigal Pharmaceuticals, and Intercept have seen their stock prices rise by double or even triple digits after positive readouts for fatty liver drugs.

Fortunately, NASH drug companies still have time to clarify market dynamics.

Unlike in other therapeutic areas, Wall Street does not expect the first or first batch of approved NASH drugs to bring significant advantages. Manufacturers and doctors hold similar views, noting that treating such a large population will require different kinds of drugs, and these drugs can be used in combination.

"It will take multiple drugs on the market and non-invasive tests to truly get about 10 million patients in the U.S. treated. That will take a long time," said Steven Seedhouse, an analyst at Raymond James, in an interview.

Although the exact size of the NASH population is unclear, hepatologists find the disease's burden in their clinics is growing. Researchersexpect it to become the leading cause of liver transplants as early as next year。

"The market is huge because obesity won't go away, hyperlipidemia won't go away. All the risk factors for NASH won't go away; they are getting worse," said Kymberly Watt, a gastroenterologist at the Mayo Clinic in Rochester.