Sometimes success just does not look like success. Enanta Pharmaceuticals’ statistical win in lowering liver inflammation markers with its Nash project EDP-305 was not enough to put clear blue water between it and the competition. After 12 weeks on the highest 2.5mg dose of EDP-305 patients in the phase IIa Aragon 1 trial saw their ALT levels fall by 12mg on a placebo-adjusted basis, similar to that seen with a low dose of Ocaliva. Strong data would have helped to convince investors that EDP-305 could stand a chance against Ocaliva, which is set to reap the advantages of being first to market if it is approved early next year. More concerning for EDP-305 were the red flags around tolerability. Enanta had previously stated that the way EDP-305 binds to FXR should avoid the pruritus that has blighted Oclaliva, but this does not seem to be the case: 21% of EDP-305 patients discontinued treatment owing to the side effect. These results do not say best in class, and if any of other next-generation FXR agonists nipping at Enanta’s heels can crack the pruritus issue EDP-305 will be firmly consigned to the also-rans.
|A cross-trial comparison: EDP-305 and Ocaliva|
|1mg||2.5mg||25mg (Flint)||10mg (Regenerate)||25mg (Regenerate)|
|Placebo-adjusted change in ALT, wk 12||10mg*||12mg||17mg||12mg||21mg|
|LDL change from baseline||+5mg/dl||+6mg/dl||+25mg/dl||+14mg/dl||+20mg/dl|
|*Not statistically significant. Source: Enanta presentation.|