Company: Intercept Pharmaceuticals
Drug name: Obeticholic acid (OCA)
Mechanism: FXR agonist
Stage: Phase 3/New Drug Application filed
Intercept’s obeticholic acid (OCA) works by modulating the farnesoid X receptor, or FXR, a nuclear receptor that regulates bile acid levels in the liver. The company already sells the drug as Ocaliva for the treatment of primary biliary cholangitis; it earned the FDA nod for that indication back in 2016. Intercept submitted OCA for FDA approval in NASH in September and plans to follow up with a European Medicines Agency filing by the end of the year.
Its regulatory submissions are based on a pivotal phase 3 study called REGENERATE, which pitted two doses of the drug against placebo in 931 patients with stage 2 or 3 fibrosis due to NASH. The highest dose of OCA, 25 mg, hit one of the study’s co-primary endpoints, improving liver scarring with no worsening of NASH at almost double the rate of placebo: 23.1% versus 11.9%. However, OCA missed its second efficacy endpoint. More patients in both OCA arms achieved NASH resolution with no worsening of liver scarring compared with placebo, but not a statistically significant number of patients. The company has since posted data from patients with stage 1 fibrosis, showing that the drug could be useful in patients with less severe scarring but who are at risk of their disease getting worse.
Despite the mixed data, Intercept was OK to move forward with its submission, as it had agreed with the FDA that the study needed to meet just one of the two primary endpoints. But others think this leaves room for competition from the crowded FXR agonist field.
“It remains to be seen whether similar agents like Enanta’s EDP-305 and Novartis’s tropifexor can improve on Ocaliva’s dubious efficacy and tolerability profile—as well as being associated with a worrying hike in LDL cholesterol levels, the drug caused more than half of patients to experience serious itching,” Vantage wrote in June.
In any case, Intercept is gearing up for a nod from the FDA as early as in the first half of 2020. It has already kicked off payer talks and hired an internal sales team to roll the drug out. Though the market already knows the drug as Ocaliva, Intercept plans to market it under a different name for NASH, CEO Mark Pruzanski, M.D., said.