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AASLD debrief: Five drugs show promise in NAFLD (and two do not)


 

REPORTING FROM THE LIVER MEETING 2019

– For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Dr. Kathleen E. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston Andrew D. Bowser/MDedge News

Dr. Kathleen E. Corey

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

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