French biotech Inventiva’s lead drug stumbles in systemic sclerosis study, ahead of NASH readout

France’s Inventiva (Euronext: $IVA) has suffered its first big setback following its public listing in 2017. The company’s lead experimental drug, lanifibranor, failed a mid-stage trial in patients with a form of systemic sclerosis (SSc) — a rare, chronic life-threatening disorder in which the immune system attacks its own organs and is characterized by a buildup of scar tissue — prompting the Daix-based drug developer to abandon the program for the indication.

The Phase IIb trial evaluated two doses of lanifibranor (800 mg, 1200 mg) against a placebo in 145 patients with diffuse cutaneous systemic sclerosis, which account for roughly 35% of the SSc population. Patients were given lanifibranor in either two doses of 400mg per day or two doses of 600mg per day over 48 weeks in addition to standard of care, which typically included immunosuppressive therapy.

Compared to the placebo, neither dose of the drug induced a statistically significant change in the modified Rodnan Skin Score — a scale measuring the evolution of skin fibrosis, which is correlated with internal scarring — missing the main goal of the study. None of the secondary endpoints, including changes in pulmonary function measured via forced vital capacity and overall progression of the disease, were met, Inventiva said on Monday.

There are no approved therapies for SSc, a disease that disproportionately affects women. According to analysts at H.C. Wainwright, the diffuse cutaneous form of the disease translates to an addressable market of about 23,500 patients in the Europe and 31,500 in the United States.

Lanifibranor is an oral small molecule designed to spark antifibrotic, anti-inflammatory changes by spurring three isoforms — α, δ and γ — of PPAR (peroxisome proliferator-activated receptor), which are nuclear receptor proteins that regulate gene expression. There are other PPAR agonists on the market (including diabetes drug pioglitazone) and in development (experimental NASH drugs such as Genfit’s elafibranor and CymaBay’s seladelpar) that target only one or two PPAR isoforms for activation, but lanifibranor is a pan-PPAR agonist like bezafibrate, which Intercept acquired last month to develop in combination with its NASH contender obeticholic acid.

Inventiva is also testing lanifibranor for NASH — a fatty liver disease affecting millions that has no approved therapies — which has thus captivated a plethora of drug developers, including Gilead $GILD, Intercept $ICPT and Genfit (Euronext: $GNFT). Inventiva’s Phase IIb trial for lanifibranor in NASH patients is expected to readout in the first half of 2020.

In a note earlier this month, H.C. Wainwright analysts suggested that positive SSc data would bode well for Inventiva’s NASH program: “(Growing) clinical evidence points to a mechanistic link between fibrotic NASH and certain inflammatory skin conditions, like psoriasis…  another anti-fibrotic agent in development for NASH, Galectin Therapeutics’ GR-MD-02, has separately reported significant improvement in patients across both plaque psoriasis and cirrhotic NASH.”

Last year, Inventiva raised raised about $44 million from a group of venture backers, including Paris-based Sofinnova, after going public in 2017 in a $51 million IPO. The company, which has programs partnered with AbbVie and Boehringer Ingelheim, was spun out of Abbott in 2012.

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