FDA Lifts CymaBay Drug Hold, Tests to Resume in Rare Liver Disease PBC

The FDA has lifted a hold on clinical trials for an experimental CymaBay Therapeutics drug in three liver diseases, clearing the way for tests to resume in all of them. But the company won’t be pressing forward in the biggest one, NASH, at least for now.

The clinical hold on the drug, seladelpar, stemmed from signs of possible liver injury in patients enrolled in CymaBay’s mid-stage studies in nonalcoholic steatohepatitis (NASH), a disease characterized by fatty buildup that leads to inflammation and scarring of the organ. The drug was also being tested in two rare liver diseases, primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The FDA’s halt to clinical testing last December extended to those indications as well.

An independent analysis conducted earlier this year concluded that there was no evidence of liver injury related to the CymaBay drug, which paved the way for the FDA’s decision Thursday to lift the clinical hold. Newark, CA-based CymaBay says its initial focus will be advancing the drug to a Phase 3 study in PBC.

Shares of CymaBay opened at $4.65 apiece, up 32 percent from Wednesday’s closing price.

PBC damages the bile ducts of the liver. The standard treatment for the disease is ursodeoxycholic acid (UDCA). Intercept Pharmaceuticals (NASDAQ: [[ticker:ICPT]]) drug obeticholic acid (Ocaliva) is approved as a second option when UDCA isn’t enough, or for patients who can’t tolerate UDCA. SVB Leerink analyst Thomas Smith wrote in a Thursday research note that the CymaBay drug could be a worthy competitor, with initial data suggesting it could offer advantages over the Intercept drug in both safety and efficacy.

CymaBay’s decision to focus on PBC was expected because the unblinded data from the earlier studies can still support a submission seeking approval, Smith added. Timing and money are also considerations. Testing in the rarer PBC will involve hundreds of patients compared to the more prevalent NASH, which calls for a pivotal study enrolling thousands, taking several years to complete. Also, despite being cleared of showing injury in the NASH study, seladelpar’s efficacy data has blemishes. Prior to the clinical hold, the company last year reported preliminary Phase 2 data showing that its drug failed to beat a placebo in reducing liver fat.

The clearance for CymaBay to resume tests of seladelpar comes at a turbulent time in drug development for NASH, a disease that is growing in tandem with rising obesity rates. Last month, the FDA rejected Intercept’s application seeking approval of obeticholic acid in NASH, dealing a setback to a drug once regarded as a frontrunner to become the first approved drug for the disorder. That regulatory decision followed the Genfit (NASDAQ: [[ticker:GNFT]]) announcement in May that its NASH drug, elafibranor, failed to beat a placebo in a pivotal study.

After the markets closed on Wednesday, France-based Genfit said it would stop developing its drug in NASH and instead focus on testing it in PBC. But Genfit will continue to support NIS4, a blood-based NASH diagnostic intended to offer an alternative to liver biopsy. The company has an agreement with Burlington, NC-based diagnostics giant LabCorp (NYSE: [[ticker:LH]]), which provides the test for use in research. Genfit says it plans to file for approval of the diagnostic for clinical use.

Public domain photo by Flickr user Qasim Zafar