Enanta Pharmaceuticals is tearing up its nonalcoholic steatohepatitis (NASH) strategy. After getting a look at interim phase 2b data, the biotech has decided to stop the monotherapy trial and seek to outlicense its candidates for use in combinations.
Massachusetts-based Enanta has two NASH candidates, EDP-305 and EDP-297, in the clinic. Both drugs are FXR agonists, the same mechanism of action of Intercept Pharmaceuticals’ obeticholic acid, with the differences limited to changes designed to improve the potency and tissue targeting of the follow-up candidate EDP-297.
Neither candidate has done enough to persuade Enanta to continue internal development. Enanta is stopping the phase 2b trial of EDP-305 that it began last year after an interim analysis of the 12-week data.
Enanta had the option to switch its focus to its follow-up candidate. However, with a phase 1 clinical trial suggesting it is “not substantially differentiated” from EDP-305, Enanta has opted against making EDP-297 its priority. The phase 1 study “found the overall balance of activity and tolerability was comparable to that of EDP-305.”
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The data drops have persuaded Enanta to abandon internal development of the candidates. Enanta is hoping another company sees promise in the prospects, though, specifically in combination with other NASH treatments.
“We believe that the multiple mechanisms in development for NASH today, which reflect the complex pathophysiology of this disease, make it likely that a combination approach with FXR agonists will ultimately provide the optimal treatment regimen for patients,” Enanta CEO Jay Luly, Ph.D., said in a statement. Luly sees EDP-305 and EDP-297 as well positioned to play a role in combinations.
The rethink follows the FDA’s rejection of Intercept’s rival FXR agonist. When Enanta began its phase 2b, Intercept looked to be closing in on FDA approval. The question at that stage was whether Enanta could differentiate EDP-305 from its more advanced rival. Months later, Intercept’s rejection by the FDA raised the question of whether Enanta could get EDP-305 approved at all. Intercept is continuing to plug away at finding a route to market, but Enanta has decided to pull out and focus its energies on treatments for diseases including hepatitis B.