Cymabay soars as Genfit hits an itch hitch

The topline hit in the pivotal Elative study of Genfit’s elafibranor in primary biliary cholangitis means the company has salvaged something from the agent, which failed disastrously in Nash three years ago. It also validates Ipsen’s move to license the PPARα/δ agonist 18 months later. But the real winner might in fact be neither of these companies but Cymabay, developer of a similarly-acting agent. Cymabay’s stock opened up 40% today whereas Genfit’s shares sank 5% and Ipsen’s barely shifted, since the Elative data provide an opening for Cymabay’s seladelpar. Elative met its primary endpoint with a statistically significant difference in composite responders at one year – 51% versus 4% with placebo – but missed on the vital secondary of pruritus improvement, only mustering a favourable trend. It appears investors believe seladelpar can do better on the itch measure when its pivotal trial, Response, reports data in the coming quarter. And with reason: in seladelpar’s other phase 3 in primary biliary cholangitis, Enhance, 78% of patients on the 10mg dose achieved the composite response versus 13% on placebo at three months. Enhance also hit on pruritis, showing a significant 1.59-point improvement with the 10mg dose among those with moderate to severe itch at baseline.

Selected projects in development for primary biliary cholangitis
Product Company Mechanism Status
Ocaliva Intercept Pharmaceuticals FXR agonist Approved in EU and US 2016
Elafibranor Ipsen/Genfit/Terns PPAR-α/δ agonist Pivotal Elative trial hit primary but missed key secondary endpoint
Seladelpar Cymabay Therapeutics PPAR-δ agonist Ph3 Enhance trial hit, though terminated early*; pivotal Response trial could report 2023
GKT831 Calliditas Therapeutics NOX1 and NOX4 inhibitor Pivotal Transform trial could report 2024
Ocaliva plus bezafibrate Intercept Pharmaceuticals FXR agonist plus PPAR-α/γ/δ agonist Interim analysis from ph2 747-213 trial presented at Easl 2023 showed promising biomarker data; interim analysis from ph2 747-214 trial expected 2023
ASC42 Ascletis Pharma Bile acid receptor agonist Ph2 trial could report 2024
CNP-104 Cour Pharmaceutical/
Pyruvate dehydrogenase stimulant Ph1/2 trial could report 2024
*Enhance was terminated early after a safety signal was seen in a Nash trial of seladelpar; the signal was later determined to be unrelated to seladelpar. Source: Evaluate Pharma,, company websites. 

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