CymaBay touts positive seladelpar liver results
- CymaBay Therapeutics announced positive interim results for seladelpar in chronic liver disease. After spiking up to $7.48, CymaBay Therapeutics closed yesterday on $5.98, up almost 6%.
- In an ongoing low-dose Phase 2 study, patients with primary biliary cholangitis (PBC) who were at high risk of progression and were resistant to or intolerant of ursodeoxycholic acid (UDCA) showed a significant reduction in alkaline phosphatase from baseline of 35% at 5 mg and 45% at 10 mg after 12 weeks.
- The alkaline phosphatase levels fell to <1.67 times the upper limit of normal (ULN), part of the composite endpoint, in 45% of patients at 5 mg and 82% at 10 mg. There were no serious adverse events and no signal for drug-induced itching. The Food and Drug Administration has agreed to continuation beyond six months for both doses.
This data from CymaBay Therapeutics is as a result of a change in direction. Earlier studies in primary biliary cholangitis (PBC) looked at much higher doses – 50 mg or 200 mg – and while these also reduced levels of alkaline phosphatase, they were linked with cases of asymptomatic, reversible transaminase elevations so these doses were terminated.
"The data emerging from this study are impressive and support our hypothesis that lower doses of seladelpar than previously studied retain strong efficacy without raising a concern with transaminase elevations. We also see that seladelpar activity is not associated with drug-induced itch, an important benefit for patients with PBC. If these results are maintained over longer periods, we think that seladelpar could offer patients significant advantages over existing treatments," said Gideon Hirschfield, Centre for Liver Research, University of Birmingham, UK.
Seladelpar also has potential in non-alcoholic steatohepatitis (NASH), a disorder with no currently approved treatments. This is based on a Phase 1 clinical trial that has been completed in patients with mixed dyslipidemia. A PPAR-gamma agonist, seladelpar has orphan designation in the U.S. and PRIority MEdicine (PRIME) status in the E.U.
Seladelpar is likely to face competition once it reaches the market. Intercept Pharmaceuticals received accelerated approval for OCALIVA (obeticholic acid) in combinations with UDCA for PBC in May 2016, and Phase 4 studies are under way. NGM Bio is also working in the PBC field, with NGM282 in Phase 2 for PBC, as well as for NASH, primary sclerosing cholangitis and type 2 diabetes. Enanta Pharmaceuticals is developing the FXR agonist EDP-305 in PBC and NASH in Phase 1.
- CymaBay Therapeutics Statement
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