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New York - Now that new medicines promise to cure millions of hepatitis C patients in coming years, drugmakers including Gilead Sciences Inc are turning their attention to other liver diseases, with a potential market that could rival the success of statins, which generated more than $30bn a year in sales at their peak.
Several companies are working on treatments for hepatitis B, which can be controlled but not yet cured, and for fatty liver conditions caused by rising obesity, which without treatment could affect half of all Americans by 2030, according to the American Liver Foundation (ALF).
Some of the drugs will address advanced fibrosis and cirrhosis, which are the scarring that virtually all liver diseases cause without effective treatments. Each of these drugs, once approved, could reach annual sales of as much as $10bn, industry analysts said.
Most of the treatments are now in early Phase I or Phase II clinical trials, with more informative interim data on several expected over the course of the next year.
Gilead, which was first to market with its hepatitis C cure Sovaldi late last year and has been racking up about $3bn in sales each quarter, is a solid bet to be among the leaders in the next wave of liver therapies, experts said.
"The Gilead program is encouraging," said Dr Naga Chalasani, director of gastroenterology and hepatology at Indiana University Hospital in Indianapolis, who is participating in clinical trials of promising drugs from Gilead and others.
Drugmakers are working to address the fatty liver disease known as NASH, or non-alcoholic steatohepatitis. Without treatment, Nash can progress to liver-destroying cirrhosis and potentially cancer.
ALF estimates that non-alcoholic fatty liver disease, including Nash, affects up to 30% of people in the United States. It can be caused by bad diets and alcohol abuse, and has also been tied to diabetes.
"We have no treatment for that condition other than tell a patient they need to lose weight," said Dr Mauricio Lisker-Melman, director of the hepatology programme at Washington University School of Medicine in St Louis.
Intercept Pharmaceuticals has attracted the most attention. Just released final data from a mid-stage clinical trial showed its obeticholic acid halted Nash progression and improved liver scarring in primarily moderately ill patients. "For now, no one else has demonstrated an antifibrotic effect in this population, and I believe we are ahead of the pack in that sense," said Intercept Chief Executive Mark Pruzanski.
Intercept plans to begin a Phase III trial with at least 1 000 more seriously ill patients next year.
Dr. Scott Friedman, dean for therapeutic discovery at Mt. Sinai Hospital in New York, who has worked with virtually all the companies in the field, said most were first testing drugs in patients whose liver damage is not advanced.
"Gilead has sort of leapfrogged that," Friedman said, tackling more serious damage, as its simtuzumab targets fibrotic scarring directly, rather than inflammation or other drivers of disease. Reversing cirrhosis and improving liver function is "the highest bar I can think of in this business, and it would be spectacular," he said.
Gilead faces competition from several smaller companies with promising drugs in development, including Intercept, France's Genfit, Israel's Galmed, Galectin Therapeutics, Conatus Pharmaceuticals and Raptor Pharmaceuticals, specialists said.
Gilead's antibody simtuzumab blocks an enzyme called LOXL2 that is directly involved in laying down bands of collagen that form the scar tissue behind cirrhosis. The collagen bands, which result from a wide variety of assaults on the liver, including alcohol and drug abuse, cross link haphazardly to destroy the liver's architecture and function.
Gilead expects to have a strong indication of whether its drug is working when one-year data from a two-year Phase II study becomes available next year.
"We have a very active research program," said Mani Subramanian, head of liver disease clinical research at Gilead. "We're targeting everything: metabolic issues, inflammation and fibrosis directly." He acknowledged challenges faced by drugmakers trying to address more advanced liver disease: "It's been a graveyard for drugs that try to reverse fibrosis," Subramanian said.
