- An experimental drug from CymaBay Therapeutics missed the primary endpoint of a mid-stage NASH trial, cutting the stock price of the California biotech in half Tuesday morning.
- After 12 weeks of testing, there wasn't a significant difference in liver fat reduction between the patient group receiving placebo and the three groups that received some dose of CymaBay's seladelpar. There were, however, declines in several biomarkers tied to liver inflammation and injury among the seladelpar-treated patients, results the company touted as positive.
- Trial investigators will collect liver biopsy data at the study's 52-week mark, which CymaBay said will allow it to "understand whether the improvement in liver injury markers will translate into histological improvement."
While not complete, the Phase 2b data indicate CymaBay's drug isn't effective in curbing liver fat, as all three doses performed worse than placebo.
"Placebo is one heck of a drug," noted Piper Jaffray's Tyler Van Buren, who cut his price target for the company from $30 per share to $8 following Tuesday's topline readout.
Yet the primary endpoint misfire won't be what sidelines seladelpar. Rather, the 52-week histology data will likely decide its future. In notes to clients, Wall Street analysts claim that if the biomarker effects already observed can translate to improvements on liver stiffness or inflammation, then the drug may have a future.
"Our thesis on seladelpar in NASH is that there is much more to this asset in NASH than just fat reduction," Eliana Merle of Cantor Fitzgerald wrote.
Investors clearly had a different impression; CymaBay shares were down nearly 50% by noon.
In the trial, investigators observed the greatest biomarker improvements in patients taking the highest of three seladelpar doses. That group showed declines in enzymes that correspond to liver health, with lower levels indicative of a healthier liver.
Reductions in alanine aminotransferase and aspartate aminotransferase, known also as ALT and AST, are particularly promising, according to Scott Friedman, chief of the liver diseases division in the Icahn School of Medicine at Mount Sinai. Friedman previously consulted with CymaBay, but no longer does.
"On balance, I'm encouraged by the findings and the histologic findings will certainly 'tell the tale' at 52 weeks," he wrote in an email to BioPharma Dive.
"Frankly, I would have been less enthusiastic if there were a benefit on fat but not on AST and ALT, as inflammation and liver cell injury, as indicated by transaminases, is a more direct driver of fibrosis than liver fat is."
So far, only obeticholic acid from Intercept Pharmaceutical's has scored positive data in a late-stage NASH trial, and even there response rates were below 25%. The lack of comparator data makes it more difficult to evaluate NASH data sets, argues Jefferies analyst Michael Yee.
"We acknowledge the NASH space has been semi-challenging for investors as they sort out what is good and what is not and how much confidence one can have in Phase 2 data and read-through to Phase 3," Yee wrote in a June 11 note.