PDUFA date set for March 26; Ad Comm will be held for potential first approved therapy in NASH; Phase 3 results released last February
Intercept announced last week that FDA has accepted its NDA for FXR agonist obeticholic acid (OCA) in NASH and also granted priority review for the therapy.
OCA was previously designated as a breakthrough therapy by FDA, and given its potential as the first approved therapy in NASH, FDA’s decision to grant priority review is expected and welcome news. FDA has set a PDUFA date for a decision on OCA’s approval for March 26, 2020 and has already committed to holding an Advisory Committee to discuss the potential approval (date as of now undecided).
As a reminder, Intercept announced positive interim results from its phase 3 REGENERATE trial (n=2,370) of OCA in NASH in February 2019, with additional details presented at EASL 2019. OCA 25 mg (once-daily) achieved superiority on one of its two co-primary endpoints in the 72-week interim analysis: OCA 25 mg met significance on the primary endpoint of fibrosis improvement of at least one stage with no worsening of NASH (p=0.0002 vs. placebo), while trending toward improvement without reaching significance on the endpoint of NASH resolution with no worsening of liver fibrosis. Of those patients taking OCA 25mg (n= 308), 23% achieved fibrosis improvement of at least one stage with no worsening of NASH (p = 0.0002), compared to 12% on placebo (n = 311). The OCA 10mg cohort (n = 312) saw 18% of patients improve (p = 0.0446). For the missed secondary endpoint, NASH resolution with no worsening of fibrosis, the 25mg group was 12% (p = 0.1268) and the 10mg group was 11% (p = 0.1814). Importantly, (i) FDA previously agreed that only one of the two co-primary endpoints had to be met for FDA approval; and (ii) fibrosis improvement is very strongly considered the more important endpoint of the two. It remains to be seen whether Intercept will look for approval of both the 10 and 25 mg doses or just one of these doses.
Per its 3Q19 update, Intercept is expecting to file OCA in the EU in 4Q19.
Intercept is also conducting the REVERSE trial of OCA in NASH with F4 fibrosis (compensated cirrhosis). Per the company’s latest update, enrollment of the outcome cohort for the trial has been completed (n=2,500), and the trial is expected to fully complete in June 2021.
As FDA makes its decision, Intercept is in the process of ramping up preparations for the potential first therapy launch within the NASH space. The company is focusing on disease state education on early vs. advanced fibrosis and is continuing to work on potential non-invasive testing methods for NASH diagnosis (biopsies are currently required, which represent a major barrier). Conversations with payers are underway and “progressing well,” with a focus on how OCA’s ability to prevent cirrhosis and related complications may drive value for health systems. See slide below from Intercept’s 3Q19 update for more.
--by Martin Kurian and Kelly Close