Following a patient case of severe liver enzyme elevations, Inventiva is suspending its Phase III NATiV3 study in non-alcoholic steatohepatitis as Madrigal Pharmaceuticals awaits a March 14 PDUFA date.
Pictured: Doctor examining liver of male patient with ultrasound scan/iStock, RossHelen
French biotech Inventiva on Thursday announced during its 2023 earnings report that it was voluntarily suspending the screening and enrollment of patients in the Phase III NATiV3 study for its investigational oral drug lanifibranor in non-alcoholic steatohepatitis.
The decision was triggered by a patient case of severely elevated aminotransferases, which was deemed to be a treatment-related Suspected Unexpected Serious Adverse Reaction. The patient, who showed no symptoms, discontinued treatment and subsequent liver tests have been improving. Additional laboratory tests and a liver biopsy showed signs of autoimmune hepatitis.
At baseline, the patient in question had presented with non-alcoholic steatohepatitis (NASH) with stage II fibrosis and was suspected of having autoimmune hepatitis, according to Inventiva’s announcement.
Inventiva’s stock dropped around 20% in premarket trading on Friday in reaction to the news.
Despite the pause in screening and randomization, NATiV3 can continue lanifibranor treatment but with a modified monitoring schedule. As recommended by a data monitoring committee, patients must undergo liver assessments every six weeks and the study’s enrollment criteria should be changed to exclude patients diagnosed with or are predisposed to autoimmune liver or thyroid diseases.
Inventiva expects to resume screening and enrollment in four to six weeks, once it has implemented the protocol amendments. The pause will likely “extend the last patient first visit timeline for NATiV3 trial to the first half of 2024,” the biotech noted in its announcement. Prior to the pause, NATiV3 was on track to complete screening in the first quarter of 2024.
Friday’s pause will not affect the Phase IIa LEGEND trial, which is assessing lanifibranor plus Eli Lilly and Boehringer Ingelheim’s Jardiance (empagliflozin) in NASH and type 2 diabetes. LEGEND is scheduled for a topline readout in the first quarter of 2024.
Inventiva’s Phase III roadblock keeps the NASH space clear for Madrigal Pharmaceuticals, whose investigational thyroid hormone receptor (THR)-β selective agonist resmetirom is currently undergoing the FDA’s review, with a target action date of March 14. In its pivotal Phase III MAESTRO-NASH study, resmetirom significantly outperformed placebo in terms of NASH resolution and liver fibrosis improvement.
Other players in the NASH space have not been as successful. In October 2023, Akero announced that its lead candidate efruxifermin fell short of its primary endpoint in the Phase IIb SYMMETRY trial, unable to significantly reduce liver fibrosis without worsening NASH versus placebo.
Former leader Intercept exited the NASH space in June 2023 after failing to secure the FDA’s approval for its obeticholic acid tablets.
Meanwhile, Boehringer Ingelheim is seeking a slice of the yet-uncontested NASH market. Last month, the pharma put $2 billion on the line in a partnership with Chinese company Suzhou Ribo Life Science and its Swedish unit Ribocure Pharmaceuticals to advance siRNA therapeutics for NASH.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
