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With positive phase 3, Intercept to file NASH drug for approval while Inventiva faces a setback

In a crowded field of nonalcoholic steatohepatitis (NASH) hopefuls, Intercept Pharmaceuticals looks to be pulling ahead. In a pivotal phase 3 study, the biotech’s obeticholic acid (OCA) met its primary endpoint of improving liver fibrosis without any worsening of NASH after 18 months of treatment. Intercept plans to file for approval in the U.S. and Europe by the end of the year. 

The study involved 931 patients with NASH, which has no approved treatment. The patients were randomized to receive a daily dose of OCA at 10 mg or 25 mg or placebo. The highest dose of OCA improved liver fibrosis with no worsening of NASH at almost double the rate of placebo: 23.1% versus 11.9%.

However, the drug missed a second efficacy endpoint. More patients in both OCA arms compared to those on placebo achieved NASH resolution with no worsening of liver fibrosis, but not a statistically significant amount. So, it had one win, on fibrosis, one fail, on NASH resolution.

But despite the mixed data, Intercept was keen to point out that it is OK to move forward with OCA: “As agreed with the U.S. Food and Drug Administration (FDA), in order for the primary objective to be met, the study was required to achieve one of the two primary endpoints,” the company said.

Jefferies analysts, seemingly very positive on Intercept, judged the data “essentially a near best case scenario,” noting that the treatment’s safety “looks stellar and very clean.”

Serious adverse events occurred at about the same rate for all three arms: 11% for both the placebo and 10 mg groups and 14% in the 25 mg group. Three patients died—two in the placebo arm and one in the OCA 25 mg arm—but none were considered treatment-related. But there was some AEs that might hit come back to haunt the company later on: Notably, the 5% severe severe pruritus (itchy skin) and 3% hepatobiliary events in the 25mg arm.

New York-based Intercept plans to present data from the study, dubbed REGENERATE, at the International Liver Congress in April. Despite the mixed picture, Intercept was up 7% by midday Tuesday on the news, likely on the fact it could still be the first to market in NASH, a potentially multi-billion dollar market.

Though things are generally looking up for Intercept, the same can’t be said for competitor Inventiva. The French biotech raised $44 million last April to bankroll multiple pursuits including the development of its pan-PPAR activator, lanifibranor, in systemic sclerosis and NASH. But lanifibranor took a blow Monday as it missed its primary endpoint in a phase 2 trial in systemic sclerosis, an autoimmune disease characterized by a buildup of scar tissue that affects the skin and internal organs. R

Specifically, the FASST study did not meet its primary endpoint of a mean absolute change from baseline to week 48 in the modified Rodnan Skin Score, a measure of skin thickness. 

Inventiva is discontinuing work on lanifibranor for systemic sclerosis but said that the setback won’t affect its other programs. In fact, it’s ditching that program “in order to fully focus on the development of lanifibranor for the treatment of NASH” as well as the development of another asset, odiparcil. Its stock fell about 45% on the news. 

“We are disappointed by the results of the FASST clinical trial in [diffuse cutaneous systemic sclerosis], a challenging disease as evidenced by the recent failure of three other late-stage trials,” said Inventiva CEO Frédéric Cren, in a statement. “While we have decided to discontinue the lanifibranor program in SSc, we are very grateful for the dedication and commitment of patients, caregivers, investigators and our team to this program. We remain confident in lanifibranor’s unique mechanism of action and will therefore continue to move forward, as planned, with its clinical development in the treatment of NASH.”