It’s been called a “silent epidemic” that’s slowly wasting away the livers of millions of Americans while doctors have a paltry understanding of the disease and no approved treatments.
Non-alcoholic steatohepatitis, or Nash, is now in the sights of more than a dozen drugmakers. Allergan plc (NYSE: AGN) became the latest, announcing two deals to acquire Nash treatments in less than 12 hours. It’s racing companies from startup Intercept Pharmaceuticals Inc. (Nasdaq: ICPT) to giants including Gilead Sciences Inc. (Nasdaq: GILD) and Pfizer Inc. (NYSE: PFE) to reach an untapped market that could be worth $5 billion to $10 billion a year, according to a May estimate by RBC Capital Markets Corp. analyst Michael Yee.
Drugmakers are still working to determine how different components of the disease -- inflammation, scarring and metabolic changes -- interact and are experimenting with a variety of treatment mechanisms. With so many companies piling into the field, they’ll have to work to distinguish themselves.
“We’re looking for something that’s got a ‘wow’ factor,” said Alex DePaoli, chief medical officer of closely held NGM Biopharmaceuticals Inc., which has a Nash partnership with Merck & Co. “We want to develop something that pops your eyes out.”
Nash occurs when fat accumulates in the liver along with inflammation and damage, and as much as a quarter of the U.S. population may have a precursor condition, called non-alcoholic fatty liver disease. The ailment develops slowly, and patients often don’t show symptoms until their livers are heavily damaged. It’s most common in people who are overweight or have diabetes, and doctors mainly prescribe diet changes and weight loss.
While doctors need to perform a biopsy to diagnose Nash, about 6 million to 15 million people in the U.S. alone are estimated to have the condition, and about 20 percent of them will go on to develop life-threatening cirrhosis. Nash will be the leading cause of liver transplants by 2020, according to Allergan. Drugs that treat it will likely command high prices, Elizabeth Krutoholow, an analyst at Bloomberg Intelligence, said.
At the head of the race are Intercept and French biotech firm Genfit, with large trials underway. Tobira Therapeutics Inc. (Nasdaq: TBRA), which Allergan agreed to buy for as much as $1.7 billion, is preparing to recruit patients for a final-stage study. Investors are also watching for results from two of Gilead’s mid-stage trials that are expected to be presented this year.
Intercept is testing Ocaliva, already approved to treat a rare liver disease called primary biliary cirrhosis, against Nash. Interim results from a final-stage trial of 2,000 people are expected next year, with final results in 2019. A potential concern is that in an earlier trial some patients experienced itching when taking the drug, in some cases so severe that it interfered with basic activities. CEO Mark Pruzanski said in an interview that he hopes Ocaliva will become a backbone treatment, used in combination with other drugs.
Genfit is developing elafibranor, a once-a-day-treatment that raises fat metabolism and fights inflammation, to “treat the underlying cause of fibrosis,” Dean Hum, Genfit’s chief scientific officer, said in an interview.
While elafibranor failed to meet a primary goal in a mid-stage trial last year, it showed promise in a subset of patients with moderate and severe forms of the disease. A final-stage trial in 2,000 moderate and severe patients is underway, and the company may have data by late 2018.
Beyond the startup biotechs, some of the biggest companies are paying attention and ready to do deals. Merck said it will pay as much as $450 million for its partnership with NGM. Gilead, maker of the blockbuster hepatitis C drugs Sovaldi and Harvoni, bought a Nash drug from Nimbus Therapeutics LLC for $1.2 billion, including milestone payments. Before that, Gilead also bought a drug from Phenex Pharmaceuticals AG for as much as $470 million.
Gilead now has four Nash candidates in its portfolio and will have data from two later this year. The drugs target different aspects of the disease and will be developed individually, but may be used in potent cocktails. Allergan’s Tobira acquisition is the biggest so far.
Pfizer, the biggest U.S. drugmaker, may be a future acquirer. It has a NASH drug in trials and two more to be tested in humans by the end of the year. Nash is “a major priority,” said Morris Birnbaum, chief scientific officer of cardiovascular and metabolic disease. The company is trying to treat the disease in its early stages.
It won’t be easy. Along with Genfit, Tobira’s mid-stage trial failed, and Raptor Pharmaceutical Corp. ended its program.
“Data is starting to come out of studies, and a lot of confidence will be built and lost,” said Jay Luly, chief executive officer of Enanta Pharmaceuticals Inc., which will begin testing an experimental treatment in patients this year. “The same, I expect, will happen with money.”