Nonalcoholic steatohepatitis (NASH) is prevalent in the U.S. and developing countries, but under that name, is largely unknown to the general public. NASH is a liver disease similar to cirrhosis, but which occurs in people who drink little or no alcohol. It is a fatty liver disease that can cause scarring of the liver and inflammation and could be fatal. It is linked to the obesity epidemic.
There are no direct treatments for NASH aside from lifestyle changes, such as diet and exercise. Family physicians often treat the precursors to NASH in terms of pre-diabetes and cardiovascular risk factors such as overweight, high blood sugar, cholesterol and A1C. GlobalData forecasts the NASH market will hit $18.3 billion by 2026 with a compound annual growth rate (CAGR) of 63 percent across the U.S. and five major European markets.
Which explains why the biopharmaceutical industry has been focusing on this area over the last several years. And some industry watchers believe 2019 will be a year where real headway is made in drug approvals for the disease.
According to Laurent Fischer, head of liver therapeutic development at Allergan, about a third of adults in the U.S. have fatty liver with up to 12 percent having NASH. Allergan has invested heavily into the space. In 2016 the company, in a string of deals that included Tobira Therapeutics, it acquired several companies specializing in NASH.
But Allergan isn’t the only company with a major interest in NASH. Others include Regeneron and Alnylam, AstraZeneca, Merck & Company, Takeda Pharmaceutical, Gilead Sciences,Bristol-Myers Squibb and Intercept Pharmaceuticals.
Generally speaking, Intercept Pharmaceutical seems to be leading the race with its obeticholic acid (OCA). On January 7, 2019, Intercept provided updates on two of its NASH programs. It expects it will have a top-line reading from the interim analysis of its Phase III REGENERATE trial in obeticholic acid in non-cirrhotic NASH patients with advanced liver fibrosis in the first quarter of this year. It also expects to complete Phase III REVERSE trial enrollment of OCA in NASH patients with compensated cirrhosis this year.
The company also announced it had licensed from Aralez Pharmaceuticals the right to develop and commercialize bezafibrate in the U.S. for primary biliary cholangitis, a type of liver damage that can lead to cirrhosis.
NASH is a complex disease, with aspects of fatty liver, cirrhosis, fibrosis and inflammation. Douglas Johnson, in analyzing the NASH market for Seeking Alpha in late 2018, noted, “Fibrosis treatment typically centers around NASH resolution or reversal of fibrosis, while treatment for cirrhosis focuses on keeping the patient alive long enough for a liver transplant to be conducted.” As such, he tends to split off and analyze the NASH fibrosis market separately than the NASH cirrhosis market.
And, in fact, many companies treat the disease as multifactorial, which will require a cocktail of medicines to treat different aspects of the disease.
It’s also not completely clear how physicians would respond to a NASH drug, if approved. A specific diagnosis of NASH requires a liver biopsy. As a result, NASH isn’t diagnosed during a routine physical exam, although many of the factors leading to it are.
In response to that, Allergan’s chief executive officer, Brent Saunders, told the Wall Street Journal, “Everybody is getting into the swimming pool, but no one has built the diving board.”
There are less invasive methods of diagnosis being developed, but they may come after a drug approval, which could make for a slower market acceptance. And, as mentioned earlier, NASH patients typically overlap other metabolic health problems like diabetes.
In December 2018, the FDA issued draft guidance for biopharmaceutical companies on developing therapies for NASH with liver fibrosis. The agency wrote, “Currently, there are no approved drugs for the treatment of NASH. Given the high prevalence of NASH, the associated morbidity, the growing burden of end-stage liver disease, and the limited availability of livers for organ transplantation, FDA believes that identifying therapies that will slow the progress or, halt, or reverse NASH and NAFLD will address an unmet medical need.”
NAFLD stands for non-alcoholic fatty liver disease.
Although Intercept appears ahead, Gilead Sciences, GENFIT and Allergan all have NASH products in Phase III clinical trials. However, in a November 2018 article, Steven Seedhouse, an analyst with Raymond James, told BioPharma Dive, “None of these drugs are so effective that it is clearly going to own the market. There’s room to improve on response rates and, because most of these drugs are pills, there’s room to combine them.”