The fatty liver disease NASH has been a tough disease target for drug developers, as shown by several high-profile clinical trial setbacks in the past year. But Gilead Sciences and Novo Nordisk see enough promise from their partnership to justify proceeding with tests of their drug combinations in a larger mid-stage study.
The companies have been testing Novo Nordisk’s approved diabetes drug, semaglutide (marketed as Ozempic), by itself and in combination with two experimental Gilead drugs, cilofexor and firsocostat. Last November, Gilead and Novo Nordisk reported Phase 2a data showing that the 108-patient clinical trial met the main goal of showing that the drugs were well tolerated.
They added that further analysis showed study also achieved exploratory goals, showing improvements in liver fat and liver injury in the combination treatment groups compared to the group given semaglutide alone. Now Foster City, California-based Gilead and Novo Nordisk, which is headquartered in Denmark, want to see if those effects hold up in a larger study.
Nonalcoholic steatohepatitis, or NASH, is a fatty liver disease that leads to scarring and liver damage. NASH has no FDA-approved treatment and in severe cases, can progress to the point where patients need a liver transplant. Like diabetes, NASH is associated with obesity and sugary diets. Some drug developers have been evaluating whether diabetes drugs can help NASH patients.
The planned Phase 2b study will evaluate the Novo Nordisk and Gilead Sciences drugs in NASH patients whose liver has deteriorated to compensated cirrhosis, meaning that the organ is scarred but still able to function. The four-arm study, which will enroll about 440 patients, is expected to begin recruitment in the second half of this year. The goal of the test will be to show improvement in fibrosis, or scarring, of the liver.
Gilead and Novo Nordisk began working together in NASH in 2019. That alliance was struck months after Gilead reported preliminary results showing that its lead NASH drug candidate at the time, selonsertib, failed to beat a placebo in improving liver scarring.
Middling clinical data has extinguished hopes of other NASH drug developers. Last May, France-based Genfit reported Phase 3 data showing that its drug, elafibrinor, did not show a statistically significant difference in helping NASH patients compared to a placebo. The following month, the FDA rejected Intercept Pharmaceuticals NASH drug candidate obeticholic acid and asked the New York company to submit more safety and efficacy data. And last July, the FDA lifted a clinical hold placed on a mid-stage study testing a NASH drug from Cymabay. But the Newark, California-based biotech elected to proceed with clinical tests of the drug in a different liver disorder.
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