Intercept’s NASH Approval Timeline Shuffled Again With FDA Delay
Executive Summary
The company said a planned 9 June advisory committee to review the NDA for obeticholic acid in NASH has been postponed a second time, which means OCA likely will not be approved by 26 June.
The picture for Intercept Pharmaceuticals Inc.’s obeticholic acid (OCA) and the expected first approval of a drug for non-alcoholic steatohepatitis (NASH) grew hazier on 22 May when the company said a US Food and Drug Administration advisory committee review planned for 9 June has been postponed following the agency’s request for more data. Intercept said it will submit the information in the next week, but an approval decision for OCA likely will occur after the new drug application’s 26 June action date.
This is not the first delay on the road to approval for OCA – a farnesoid X receptor (FXR) agonist that was the first drug to post successful Phase III data in NASH last year. The initial action date was pushed back 90 days last December from 26 March to 26 June, to allow for an advisory committee then expected on 22 April. (Also see "Intercept’s NASH NDA Positions OCA For May 2020 Approval, Then Launch" - Scrip, 30 Sep, 2019.) That schedule got thrown into further disarray with FDA’s announcement in March that all internal meetings scheduled through the end of April would be postponed due to the COVID-19 pandemic. (Also see "Could Postponement of Intercept’s Expected NASH Panel Impact Its PDUFA Date?" - Scrip, 10 Mar, 2020.)
The FDA never officially announced an advisory panel review of OCA on either of those dates. Intercept said on 22 May, however, that the agency pledged it would “reach out” in the near future with a new proposed date for the advisory committee.
The user fee action date for a decision on OCA in NASH will not be rescheduled as FDA regulations allow only one major amendment and extension for a new drug application. This means the likeliest outcomes for Intercept now are either a rescheduled advisory committee and approval of OCA sometime after 26 June or a complete response letter, which could dramatically change the drug’s potential to be the first-to-market treatment for NASH.
Intercept is seeking approval for OCA as a treatment for advanced fibrosis in NASH patients. In the Phase III REGENERATE clinical trial, the drug met statistical significance on a primary endpoint of fibrosis reduction from baseline and missed a co-primary endpoint of NASH resolution, but statistical significance on only one endpoint was needed for the trial to be deemed a success. (Also see "Intercept Retakes The Lead In NASH" - Scrip, 19 Feb, 2019.)
OCA – approved under the brand name Ocaliva in 2016 as a treatment for primary biliary cholangitis – long has been poised to become the first approved drug for NASH, a position only strengthened when Intercept’s closest pursuer, Genfit SA, revealed on 11 May that its candidate elafibranor failed its Phase III trial. (Also see "RESOLVE-IT Failure Dashes Genfit's NASH Hopes" - Scrip, 12 May, 2020.)
Analysts Think OCA Still On Track, But Want Details
After this latest development, analysts generally took the position that while this additional timeline change creates uncertainty around approval of the NDA, it might only mean a temporary setback for Intercept. Jefferies analyst Michael Yee posited on 22 May that the advisory committee might not occur until sometime in July, with the approval potentially coming 90 days after the current action date.
Jefferies is not revising its probability scenarios for OCA in NASH, Yee said, expecting that the drug will get approved this year. “We argue Intercept is still generally fine and this is about a totally new indication and accelerated approval on a new endpoint,” he wrote. Yee noted that near-term revenue projections for OCA have been decreasing, but that the launch might fare better in some ways if it occurs another three months past the hoped-for end of the COVID-19 pandemic.
Morningstar is maintaining a 75% likelihood of approval for OCA in NASH. “At best, this pushes back the launch by several weeks,” analyst Anna Baran wrote on 22 May. “At worst, this is an indication that the FDA has doubts regarding OCA’s efficacy and safety.”
Informa's Biomedtracker left its 93% likelihood of approval unaltered following the 22 May announcement.
Intercept offered no detail about what additional information it is readying for the FDA, and analysts from SVB Leerink and Credit Suisse both said clarity about that might address investors’ concerns. Intercept’s share price fell during the trading day, closing down 12% at $80.51 on 22 May.
“While today’s news will drive [share price] volatility short-term, and greater clarity on the additional data request would’ve been welcomed, we believe fundamental impact from today’s update is likely limited,” Credit Suisse’s Tiago Fauth said. “[We] continue to believe Intercept’s data has established a compelling benefit/risk profile in the indication and targeted commercial population.”
Leerink analyst Thomas Smith speculated that the additional data the FDA requested might be broad-based, however, citing efficacy, safety, non-invasive testing, benefit/risk and risk management as likely subjects. “Today’s delay, in our view, injects additional uncertainty into the FDA panel discussion and potential approval/label/timing,” he wrote on 22 May.
Smith speculated that advisory committee discussion topics probably will include the clinical relevance of the REGENERATE data, the implications of a failed OCA NASH study in Japan, safety and tolerability issues pertaining to LDL cholesterol levels and pruritus, optimal dosing of OCA and whether the label might require liver biopsy for diagnosis of patients. A biopsy requirement in the label could hinder OCA launch’s momentum, analysts have warned.