- Gilead and Novo Nordisk will continue testing combinations of Novo's diabetes shot Ozempic with two experimental Gilead drugs to determine if the regimen can help reverse liver damage in patients with nonalcoholic steatohepatitis, a disease commonly known as NASH.
- The two companies announced Thursday they would extend a deal forged in 2019 after the three-drug combination proved safe and showed signs that it helped resolve the disease. A Phase 2b trial in 440 advanced NASH patients will start later this year and test Novo's Ozempic alongside a fixed-dose pill containing the Gilead medicines cilofexor and firsocostat.
- Gilead is trying to reinvigorate its NASH strategy after the failure of its most advanced project, selonsertib. Setbacks for other rivals in this space, however, including onetime leader Intercept Pharmaceuticals, means the partners could be among the first to market with drugs for a disease thought to affect millions of people.
Novo's Ozempic comes from a class of diabetes drugs called GLP-1 agonists, which help stimulate insulin to help keep blood sugar under control. In addition to diabetes, some of them — such as Novo's Saxenda — are also approved in obesity.
The drugs' metabolic effects may also help patients with NASH, a fatty liver disease linked to sugary diets. Obesity, diabetes and other related metabolic symptoms such as high cholesterol are all risk factors for NASH, so bringing them under control may help those whose livers have already been damaged.
A 0.4 milligram dose of Ozempic's active ingredient, semaglutide helped clear up patients' NASH and stopped liver scarring in a Phase 2 trial. Meanwhile, Novo's diabetes rival Eli Lilly is testing its next-generation GLP-1 drug tirzepatide in NASH. Academic investigators are also examining Lilly's marketed medicine Trulicity in patients with NASH and diabetes.
After Gilead and Novo reported positive safety data for combinations of Ozempic, cilofexor and firsocostat in their Phase 2a trial, they looked at signs of that the disease might be resolving. They found a measure of disease reduction on imaging scans in patients who got all three drugs when compared to Ozempic alone, as well as less liver damage.
The Phase 2b trial the two companies are planning will test the regimen in sicker patients who have progressed to an early form of cirrhosis. The four-arm study, which will randomize some patients to receive a placebo, will measure whether liver scarring improves and NASH is cleared up.
The odds are against Gilead and Novo, however. While the number of patients with NASH is expected to grow in coming years as a result of the obesity epidemic, developing a drug for the condition has proven a major challenge.
Intercept's obeticholic acid, marketed as Ocaliva for a separate liver disease, led the field for years on the basis of a positive Phase 2 study. But the FDA rejected Intercept's attempt at a speedy approval in 2020 and asked for more data. Intercept's shares have plummeted since, and multiple top executives have left the company.
Other drugmakers have had a tough time in NASH as well. In addition to Gilead's own setback, the French company Genfit shelved a drug called elafibranor after a trial failure.
Another drug called cenicriviroc has struggled to show it helps NASH patients. That drug is now owned by AbbVie, and is still listed in active development for NASH, but has gotten more interest as a treatment for COVID-19 in the past year.