Last year, Albireo CEO Ron Cooper painted elobixibat, a drug approved in Japan for constipation, as one arm of a two-pronged strategy to fight fatty liver disease. Now, the company is down to one prong, as the program failed to move the needle on nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) in a phase 2 study.
Make no mistake—the study actually did hit its primary endpoint, with elobixibat doing nearly twice as well as placebo at lowering LDL, or “bad,” cholesterol, logging a 20.5 mg/dL decrease compared to an 11.1 mg/dL decrease. But it fell short where it mattered, turning up “unremarkable results” on measures important to NASH, including lowering liver enzyme levels and cutting liver fat as seen by MRI.
The phase 2 study pitted a daily dose of elobixibat against placebo in 47 adults who had NASH confirmed by liver biopsy, or a suspected NASH or NAFLD diagnosis. About half of the patients—57% in the elobixibat group and 46% in the placebo group—were taking cholesterol-busting drugs.
The elobixibat group saw “no meaningful change” in levels of a liver enzyme called ALT and posted just a 2.6% decrease in liver fat. Both groups experienced side effects at about the same rate, with no serious effects reported. No patients quit the study because of side effects.
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“We wanted to investigate the potential of elobixibat in NASH and allocated minimal resources to an exploratory phase 2 study. Based on the results of this study, we have made the decision not to pursue further development of elobixibat in NASH,” Cooper said in a statement on Tuesday.
Albireo decided to test the constipation med in fatty liver disease in the hopes that inhibiting the ileal bile acid transporter (IBAT) could improve various issues, such as scarring and inflammation in the liver, as well as elevated bile acids, fat and glucose. The FDA cleared the phase 2 study in April 2019.
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Moving forward, the company will keep plugging away at its lead program, odevixibat, which is in phase 3 for biliary atresia, a condition that affects infants in which the bile ducts are scarred and blocked, and a progressive liver disease called progressive familial intrahepatic cholestasis, or PFIC, which typically leads to liver failure. It is also developing odevixibat for children’s liver diseases, such as Alagille syndrome, a genetic condition that can cause people to have fewer bile ducts than normal, which can lead to liver scarring and damage thanks to bile buildup in the liver.
Behind odevixibat, it has a preclinical “lead candidate” in the works for adult liver disease, as well as a program designed to modulate bile acid for an undisclosed indication. A third program, dubbed A3384, is in a phase 2 study in bile acid malabsorption disease.