One of the Last Untapped Blockbuster Diseases? Drug Companies Race to Find a Cure

The next frontier for multibillion-dollar drug therapies is a silent disease many people don't know they have.

Dozens of pharmaceutical companies including Gilead Sciences Inc., Allergan PLC and Intercept Pharmaceuticals Inc. have joined the fray to bring a treatment for nonalcoholic steatohepatitis -- a common but often undetected fatty-liver disease -- to market. Interest in the disease, known as NASH, has spurred at least six deals over two years valued at $3.52 billion or more.

Overall, more than 40 drugs in mid- and late-stage trials are targeting various aspects of the complex metabolic disorder.

NASH is the progressive form of nonalcoholic fatty-liver disease. Fat buildup causes inflammation, cell damage and eventually fibrosis.

The companies are lured by the promise of a large and growing pool of patients for whom there is currently no treatment. As much as 12% of the U.S. population is believed to have the disease, which is linked with other metabolic conditions on the rise including obesity and Type 2 diabetes, according to the National Institute of Diabetes and Digestive and Kidney Diseases. NASH generally has no symptoms early on but can lead to cirrhosis and liver cancer.

SunTrust Robinson Humphrey's analyst Edward Nash, who has called NASH "one of the last untapped multibillion-dollar therapeutic areas," forecasts the space to grow to more than $5 billion in the U.S. alone by 2028. Research and consulting firm GlobalData estimates the NASH space across seven major markets -- the U.S., France, Germany, Italy, Spain, the U.K. and Japan -- is set to rise to $25.3 billion by 2026.

As markets for diseases such as diabetes and hepatitis C become crowded, companies are looking to NASH for their next big break.

With so many players chasing the market, some analysts are concerned there aren't enough patients to support multiple treatments. A definitive diagnosis requires an invasive biopsy, and awareness of the disease is low. At least two companies have disclosed issues filling their drug trials.

Pricing could also come under pressure from payers that have experience playing hepatitis C drugs against each other to win rebate concession. A drug would need to demonstrate clear clinical benefit over rivals to command premium pricing.

But companies say it is likely different treatments will be used in combination to treat patients in different stages of the disease. Some drugs attempt to reduce fat in the liver while others aim at symptoms such as inflammation and fibrosis, or scarring of the liver. Some drugs address combinations of these.

"This is a race," says Mark Pruzanski, chief executive of Intercept, which has one of the drugs furthest along in development. "But it's not a zero-sum game."

Drug-company interest got a boost in January 2014, when the NIH halted a clinical trial of Intercept's drug obeticholic acid in NASH patients because the drug significantly improved measures of liver health versus a placebo. That disclosure nearly quadrupled Intercept's market value, though it ebbed amid reports of the drug's effects on cholesterol levels.

Results from a study released later that year eased concerns over cholesterol and the company's stock surged again.

"Those positive results suddenly lit a fire under the field and woke people up to the possibility that this is an untapped market," said Scott Friedman, liver-disease chief at the Icahn School of Medicine at Mount Sinai Hospital in New York.

Intercept had an early advantage because its obeticholic acid, whose brand name is Ocaliva, is already approved for another liver disease. Mr. Pruzanski said Intercept intends to position the drug as the first-line treatment to which others can be added.

Other companies say they have their own particular edge.

In September, Allergan snapped up Tobira Therapeutics Inc. and Akarna Therapeutics Ltd. for $1.7 billion and $50 million, respectively, adding a trio of NASH therapies to its pipeline. It also is collaborating to combine one of its drugs with one of Novartis AG's liver treatments, which is in phase 2 trials.

A Novartis spokesman said the company believes combination therapy that treats both the metabolic and fibrotic components of NASH will be critical.

"NASH is not a single disease for everybody, it manifests differently," said Allergan's chief medical officer, Gavin Corcoran. "We'd like to have different series of therapies that have been tested together."

Gilead last year bought Nimbus Therapeutics LLC's liver-drug program and now also has three NASH candidates in its pipeline. Mani Subramanian, senior vice president of liver-disease therapeutics at Gilead, says the company's program is aimed at patients in the later stages of sickness, where the liver is scarred and losing function.

"It is by far the biggest clinical need because it's what leads to mortality," he said.

Mike Burgess, Bristol-Myers Squibb Co.'s head of cardiovascular, fibrosis and immunoscience development, insists the company's phase 2 candidate has the trifecta: It reduces fat in the liver and is anti-inflammatory and antifibrotic. He says it also addresses issues outside of NASH, such as increasing insulin sensitivity in patients who are diabetic.

Much will depend on identifying patients with the disease. Right now, diagnosis is often by chance.

Diabetes and heart disease run in Robin A. Rothman's family, so she has been careful to keep a close watch on her health. She was diagnosed with NASH three years ago, after an episode with hives, and her doctors initially suspected hepatitis C because her partner had the virus.

The 45-year-old Brooklyn, N.Y. resident, who has since taken off 12 pounds, has joined Intercept's latest clinical trial. The day-to-day is simple: one pill. But Ms. Rothman also volunteers to do regular blood draws and provide stool samples.

"I want them to have as much information as possible to do as much good as possible," she says.

Write to Anne Steele at

(END) Dow Jones Newswires

June 23, 2017 07:14 ET (11:14 GMT)