Genfit is stepping up combination trials for its non-alcoholic steatohepatitis (NASH) candidate elafibranor, perhaps recognising the challenges of treating this complex disease.
The French biotech says it has identified “multiple” compounds that could be used alongside its lead drug – a dual PPAR alpha and delta agonist – which is already in a pivotal phase 3 trial called RESOLVE-IT due to generate results before the end of the year.
Genfit says it plans to launch a 24-week proof-of-concept study in the second half of this year to evaluate the combination of elafibranor with a GLP-1 receptor agonist plus a combination with an SGLT2 inhibitor, to try to offer “optimal benefits” to NASH patients.
The decision comes after mixed fortunes for some of Genfit’s rivals in the race to develop an effective therapy for NASH, one of the hottest targets in biopharma at the moment
It’s notable that Gilead now has a two disappointing late-stage trial readouts for its ASK1 inhibitor selonsertib in NASH, while front-runner Intercept is pitching its candidate Ocaliva (obeticholic acid) to the FDA, despite somewhat lacklustre phase 3 data and some tolerability concerns.
Genfit insists it is still confident that elafibranor could be the first monotherapy to be approved by regulatory agencies for resolving NASH, which generated promising results in a phase 2b trial, but its new programme points to a growing sense that multiple pathways may have to be targeted to have a robust impact on the disease.
Despite the recent interest in the category, non-alcoholic fatty liver diseases such as NASH are still an emerging therapeutic area with incomplete scientific understanding of the pathological mechanisms that underpin them.
NASH, which is characterised by a build-up of fat and scarring in the liver, is thought to afflict up to 50 million people in the US, in many of them as consequence of obesity and diabetes. Some estimates put the market potential at more than $20bn.
“Combined metabolic mechanisms could offer optimal benefits by addressing the underlying drivers of NASH disease progression and its downstream consequence, fibrosis, through complementary pathways,” said Genfit in a statement.
The new study will test a 120mg dose of elafibranor – the same dose on trial in RESOLVE-IT – with the undisclosed GLP-1 and SGLT2-targetng drugs, and recognises the close relationship between NASH and cardiometabolic diseases, says Genfit.
It will enrol patients with suspected NASH and significant to advanced fibrosis, measured using non-invasive diagnostic tools including Genfit’s own NIS4 diagnostic test for NASH.
Dean Hum
“NASH is a multifaceted cardio-metabolic disease affecting the liver, the cardiovascular system, and a driver of systemic decline,” commented Genfit’s CEO Dean Hum.
“Like in diabetes, over time, optimal treatments will likely combine several molecules with already proven efficacy and clean safety as stand-alone therapies.”