FDA lifts hold on CymaBay’s NASH drug, but the company may still leave the ailing field
Eight months after a single trial readout blew up their NASH program, their stock price and put development around their lead compound on indefinite hold, CymaBay has been cleared to get back to work.
The FDA has lifted the clinical hold it placed on the company and their experimental seladelpar last year after planned biopsies for their NASH trial revealed “atypical histological findings” — a phrase that here means the drug, rather than reducing patients’ liver fat, appeared to lead to liver damage. The Phase IIb trial was terminated, along with a Phase IIa for primary sclerosing cholangitis (PSC). Studies on primary biliary cholangitis were put on hold. SVB Leerink called it “a worst case scenario” and the stock fell from $5.55 to $1.89.
CymaBay said that an expert panel they convened after the trial readout found “no clinical, biochemical, or histological evidence” that seladelpar was injuring patients and “unanimously supported” re-initiating the trials. The FDA lifting the hold allows the company to proceed with 3 trials testing the drug in NASH, primary biliary cholangitis and primary sclerosing cholangitis.
It doesn’t appear that they will proceed with all of them, though. Even if the drug wasn’t harming NASH patients in that trial, the company is still left with the fact that the drug didn’t appear to be helping either. CymaBay didn’t say they were abandoning NASH, but the indication — a potential blockbuster market that once floated CymaBay’s stock – was conspicuously absent from CEO Sujal Shah’s remarks.
“This is a pivotal event for seladelpar, which had garnered a high degree of patient interest based on its promising potential for anti-cholestatic, anti-inflammatory and reduced symptom burden in patients with PBC,” he said. “We are gratified and energized to be able to once again advance seladelpar into a registrational program to confirm its benefit. It is our unwavering goal to one day make it available to patients with PBC, and potentially for other chronic, inflammatory liver diseases.”
CymaBay’s stock rose 32% on the news, from $3.51 to $4.66.
SVB Leerink’s Thomas Smith said the decision to start with PBC was no surprise, given they’ve already generated blinded Phase III data and the fact that the remaining clinical work for PBC likely requires following several hundred patients for a year, as opposed to thousands of patients over multiple years for NASH.
“Importantly, this regulatory update removes a key regulatory overhang, and should alleviate some investor concerns regarding both the timing and nature of the FDA’s response to the independent panel findings,” he wrote in a note to investors. “This is a critical step forward in resuming seladelpar clinical development, and we expect strength in CBAY shares this morning.”
Prior to the hold, CymaBay had been running a Phase III trial in PBC, a chronic disease that slowly destroys bile ducts in the liver. That trial will now proceed. A Phase II trial readout last year showed 5 mg and 10 mg doses of the drug led to a 36% and 43% reduction in alkaline phosphatase, a chemical biomarker for the disease.
In an email, Shah said that although they’re beginning with PBC, the company continues to see potential in NASH. “NASH is a complex, heterogeneous disease and while we are encouraged by the effects of seladelpar in NASH, particularly on fibrosis, there is more work to be done around the right development strategy (e.g. combinations) that should be explored,” he said.
As recently as the winter of 2019, the field was considered to be one of the next blockbuster markets for pharma, but a series of big trial failures, including CymaBay’s, have crippled expectations. Genfit, once one of the leading NASH biotechs, announced yesterday they were terminating the program after a Phase III failure.