US-based clinical-stage biopharmaceutical company CymaBay Therapeutics has announced plans to initiate the next Phase 2 study of MBX-8025 in subjects suffering from primary biliary cholangitis (PBC).
PBC is an autoimmune disease of the liver, characterised by impaired bile flow (cholestasis) and accumulation of toxic bile acids. There is also an accompanying inflammation and destruction of the intrahepatic bile ducts, which can lead to fibrosis, cirrhosis and liver failure.
MBX-8025 is an orally administered potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, a nuclear receptor important for lipid transport, storage and metabolism in liver and muscle.
An initial Phase 2 study of MBX-8025 has been terminated when proof-of-concept was demonstrated by marked improvements in biochemical markers of cholestasis, including alkaline phosphatase (ALP), a surrogate biomarker that has been associated with clinical outcomes in PBC.
The study also identified a treatment-emergent signal of transaminase elevations.
Following discussions with US FDA authorities, the company will initiate a second Phase 2 study that will probe lower doses of MBX-8025 in subjects with PBC to optimise the response.
The study is expected to commence by the end of this year.
CymaBay Therapeutics president and chief executive officer Harold Van Wart said: “We are very pleased that the next steps in the development of MBX-8025 for PBC are now clearly defined.
“Having established a clinical proof-of-concept, we can now focus on dose selection to optimise the response in the next study.
“Based on the magnitude of the ALP lowering observed in our earlier Phase 2 study and the fact that MBX-8025 does not appear to cause pruritus, we are eager to explore a lower dose range.”
CymaBay’s MBX-8025 has been granted orphan drug designation as a treatment for HoFH and Fredrickson types I and V hyperlipoproteinemia.