A new formulation of Bausch Health’s Xifaxan (rifaximin) has failed to demonstrate efficacy in two Phase III studies in hepatic encephalopathy (HE) – a setback to the company’s hopes for a new version of its flagship antibiotic.
The placebo-controlled trials evaluated the potential of amorphous-rifaximin solid soluble dispersion (SSD) to delay the onset of the first episode of HE in adults with liver cirrhosis – collectively enrolling more than 1,000 patients across 17 countries.
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In both the RED-C-3131 and RED-C-3132 studies (NCT05071716; NCT05297448), rifaximin SSD failed to significantly delay the first onset of HE in the treatment group compared with placebo, missing its primary endpoints.
Bausch Health’s stock value dropped by more than 10% from $6.57 at market close on 22 January to $5.91 at the same time on 23 January following the news debut.
While Bausch divulged information about the drug’s performance in primary endpoints, it remains unclear if the drug met any of its key secondary endpoints, which include time to all-cause hospitalisation and time to first confirmed overt hepatic encephalopathy (OHE) requiring medical intervention.
HE is a common and severe neurological side effect of liver cirrhosis, where patients experience symptoms of mild cognitive impairment, as well as confusion and sleep disturbances due to a buildup of toxins in the brain. If left untreated, it can be fatal. No preventative therapies have yet gained approval for HE triggered by liver cirrhosis. Researchers currently estimate that HE occurs in as many as 40% of patients with liver cirrhosis, which approximately impacts one in 400 people across the US.
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By GlobalDataIn a 23 January statement, Bausch’s CEO Thomas Appio noted that while the company was “disappointed” by the results of the late-stage studies, it would continue to review the datasets from both trials to identify any new development opportunities for rifaximin SSD.
Bausch’s rifaximin was first approved in the US under the brand name Xifaxan for traveller’s diarrhoea in 2004. Since then, it has received label expansions for the reduction in risk of OHE recurrence in adults and for the treatment of irritable bowel syndrome with diarrhoea in adults. Xifaxan is Bausch Health’s primary revenue driver, though the drug is poised to lose patent protection in 2029.
HE’s clinical landscape
Massachusetts General Hospital and the Schulan (Hangzhou) Hospital are currently evaluating the role of faecal microbiota transplantation in treating HE through their own respective Phase II trials. (NCT03420482; NCT05669651). According to GlobalData’s Pharmaceutical Intelligence Center, there are six clinical-stage trials looking into the therapeutic potential of microbiome components such as faecal bacteria or strains commonly found in the gut microbiome.
Others are looking into the potential of mesenchymal stem cells in this indication, including the First Affiliated Hospital of Fujian Medical University and the Chinese Military Hospital 302.
Swedish pharmaceutical company Umecrine Cognition previously posted promising results from a pilot study on its GABA-A receptor-modulating steroid antagonist, golexanolone, in HE – though the company paused its development in this indication to prioritise its progression in primary biliary cholangitis (PBC).
Meanwhile, in the world of medtech, eGenesis is testing its genetically engineered pig liver plus OrganOx’s extracorporeal liver cross-circulation (ELC) system in an early-stage trial involving patients with acute-on-chronic liver failure (ACLF) and HE. The combination is designed to either support a patient’s liver enough for it to make its own recovery or to provide time for patients as they wait for a liver transplant.
