A panel of FDA advisors gave a thumbs-up today to obeticholic acid, a drug from New York-based Intercept Pharmaceuticals (NASDAQ: [[ticker:ICPT]]) that the agency is considering as a treatment for a rare autoimmune liver disease. The outside advisors, mainly medical specialists from around the U.S., recommended that the FDA approve obeticholic acid, or OCA, by a unanimous 17-0 vote.
The FDA decision is due by May 29, but the advisory meeting today is sure to stoke speculation about OCA’s use to treat nonalcoholic steatohepatitis, or NASH, a much more common liver disease that has been driven in recent years by the obesity epidemic.
To be clear, the data under the microscope today come only from tests of obeticholic acid in people with primary biliary cirrhosis—a rare disease in which the immune system attacks the liver—not NASH. But both conditions lead to similar outcomes: scarring of the liver that eventually requires a liver transplant. But transplants are risky surgeries, and not readily available. There are about 17,000 patients waiting for transplants and only 5,000 livers available, according to the American Liver Foundation.
Transplants don’t always work, as one woman with PBC told the panel. She recounted the story of her younger sister who also had PBC, went through two liver transplants in two months, and died in the intensive care unit as her family played Bruce Springsteen and said their goodbyes. “Itching, fatigue, I have learned to live with those things,” the woman told the panel, referring to side effects that have been tied to OCA. “They’re not going to end my life, and they didn’t end [my sister’s] life. Liver damage killed [her].” The woman advocated for OCA as a treatment that might be able to address liver damage. “I would live the rest of my life with pruritus [itching] and fatigue if I knew I could extend the life of my liver,” she said.
The panel voted yes despite some panelists’ reservations that there’s no direct proof OCA makes people better. The FDA asked the panelists to debate whether an enzyme, alkaline phosphatase (ALP), that OCA does a good job reducing is a “reasonably likely” predictor of a better health outcome. “It’s not the best [marker] but it’s the best we have,” one panelist said.
FDA can greenlight drugs based on surrogate endpoints, as such predictors are called. Putting off an approval decision until a drug shows an effect on a slow-moving disease can be impractical.
The FDA approved two next-generation cholesterol drugs last year, known as PCSK9 inhibitors, based on their ability to reduce bad cholesterol. But the drugs have not yet been shown to actually improve health outcomes, and insurers are proving extremely stingy in paying for their use. Instead, they are waiting for the drug makers, Regeneron Pharmaceuticals (NASDAQ: [[ticker:REGN]]), Sanofi (NYSE: [[ticker:SNY]]), and Amgen (NASDAQ: [[ticker:AMGN]]), to reveal results of those longer-term, expensive outcome trials in the next year or two.
Panelists were also on board with the way Intercept wants to administer the drug, starting with a 5mg daily dose (OCA is given as a pill) then moving to 10mg after several months once a patient seems to tolerate the drug. One note of caution was the incidence of liver-related “events,” or unusual symptoms, among patients taking 10 mg of OCA. Liver problems can be a flag for regulators. The signal seemed to be mild in this case, but at least one panelist wanted assurance that the symptoms would be followed in post-approval studies if the FDA approves the drug next month.
Intercept is currently running a roughly 2,000-patient, Phase 3 trial of OCA in NASH, and expects to provide an interim look at the data next year. Several others are developing rival drugs for the disease, among them Foster City, CA-based Gilead Sciences (NASDAQ: [[ticker:GILD]]), France’s GenFit, South San Francisco, CA-based Tobira Therapeutics (NASDAQ: [[ticker:TBRA]]), and Conatus Pharmaceuticals (NASDAQ: [[ticker:CNAT]]) of San Diego. Gilead just paid $400 million up front for a NASH drug being developed by Nimbus Therapeutics of Cambridge, MA.
Shares of Intercept were halted on Thursday, but climbed about 11 percent, to $183.10 apiece, in post-market trading.
