[Updated, 5/31/16, see below] The FDA ended a busy week by giving a thumbs-up late Friday to obeticholic acid as a treatment for primary biliary cirrhosis, a rare disease in which a patient’s own immune system attacks the liver.
Obeticholic acid, to be marketed under the brand Ocaliva, is being developed by Intercept Pharmaceuticals (NASDAQ: ICPT) of New York. Approval was all but guaranteed by a unanimous vote of support from a group of outside advisors to the FDA in April.
The approval arrived late Friday night, in sharp contrast to the FDA’s announcement Wednesday that it would delay judgment on eteplirsen, an experimental treatment for Duchenne muscular dystrophy from Cambridge, MA-based Sarepta Therapeutics (NASDAQ: SRPT).
The Duchenne situation has taken on political baggage. Two senators, spurred by vocal patient groups that hope to sway the agency’s final decision, have asked the FDA to overrule its scientists and advisors who have recommended the drug’s rejection.
For Intercept, approval for obeticholic acid provides fresh momentum. The company must now convince to doctors who specialize in liver disease that the drug, despite a few lingering questions from the advisors last month, is worth prescribing for PBC. The data from the clinical trials have not shown that the drug actually helps people live longer or makes their lives better.
Instead, the data the FDA relied upon showed that OCA, as the drug is called in shorthand, reduced an enzyme in the blood, alkaline phosphatase, which is linked to PBC. That link—known in clinical speak as a “surrogate endpoint”—was good enough for FDA for now. But the agency will want to see more data as OCA is prescribed in real-world conditions. Until the drug is proven in longer-term use to reduce deaths or liver transplants, insurers might be tight fisted with their coverage.
According to the FDA’s approval, OCA can be used in combination the standard of care for PBC, ursodeoxycholic acid, or as a standalone therapy for people who can’t tolerate ursodeoxycholic acid.
The surrogate endpoint problem has curtailed other drugs seemingly destined for wide use. Case in point: 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, alirocumab (Praluent) and evolocumab (Repatha), 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: REGN), Sanofi (NYSE: SNY), and Amgen (NASDAQ: AMGN), to reveal results of longer-term, expensive outcome trials in the next year or two.
Beyond PBC, Intercept wants to show that OCA deserves FDA approval to treat a much bigger group of patients, those with nonalcoholic steatohepatitis (NASH), a liver disease driven recently by the obesity epidemic.
Both PBC and NASH lead to the same outcome: cirrhosis, or scarring (pictured), and liver failure. There are 6,000 liver transplants in the U.S. each year, but 17,000 people need one, according to the American Liver Foundation. NASH could soon be the leading cause of liver transplants in the U.S. A drug that could forestall transplants or even reverse the liver damage from NASH could gain traction quickly.
Intercept isn’t the only company racing to get a NASH drug on the market. Gilead Sciences (NASDAQ: GILD) just paid $400 million for a drug from Nimbus Therapeutics that’s only been through Phase 1, with $800 million more to come if Gilead can win FDA approval. Gilead has another NASH drug in its pipeline, simtuzumab, although it recently failed to show a benefit in patients with the lung scarring known as idiopathic pulmonary fibrosis.
The French firm Genfit, with a presence in Cambridge, has a NASH drug that recently began a 2,000-patient Phase 3 trial. The company hopes to show enough for a faster review than the FDA typically allows by collecting data from roughly half the patients after 72 weeks of treatment.
And after shelving its lead drug in HIV in 2013, Tobira Therapeutics (NASDAQ: TBRA) of South San Francisco, CA, shook up management and pushed the same drug ahead instead in NASH, with a Phase 2b trial underway.
But Intercept’s OCA has made the biggest splash in NASH. The FDA granted it a breakthrough designation in early 2015, which could help speed up the review process. A worldwide Phase 3 trial is ongoing, with final data due in 2021. But Intercept, like Genfit, wants to stop roughly half way to see if the data warrant an early approval. Because those patients would only take the drug for 72 weeks before evaluation, the benefit would be based on surrogate endpoints—it’s not enough time to show actual health benefits.
[Updated with pricing information] During a conference call Tuesday morning, Intercept officials said that OCA will have a list price of $69,350. The drug will be available in seven to 10 days.