BOSTON--Albireo Pharma Inc., a clinical-stage orphan pediatric liver disease company developing novel bile acid modulators, has announced topline results from the Phase 2 proof- of-concept clinical trial evaluating elobixibat, its ileal bile acid transporter (IBAT) inhibitor currently approved in Japan for chronic constipation, for the treatment of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Following promising results in preclinical studies, the Phase 2 study achieved the primary endpoint of reduction of low-density lipoprotein cholesterol (LDL-C) but did not achieve proof-of-concept for other key NASH measures.
Elobixibat achieved the primary endpoint of a reduction in LDL-C with a clinically meaningful effect of -20.5 mg/dL in serum LDL-C compared to -11.1 mg/dL, elobixibat vs. placebo (p<0.022). These reductions were in addition to lipid lowering treatment where 56.5% of the elobixibat and 45.8% of the placebo patients were on stable lipid lowering therapy at baseline. Liver fat reduction in the elobixibat group was -2.6% as measured by MRI PDFF. The baseline alanine aminotransferase (ALT) levels were within the normal range and there was no meaningful change observed in the study. Overall elobixibat was well tolerated, with adverse event incidence similar to placebo and with no serious adverse events or discontinuations due to treatment. The study showed an acceptable gastrointestinal tolerability with 3 of 23 elobixibat patients reporting mild to moderate transient diarrhea attributable to drug treatment.
The proof-of-concept Phase 2, multicenter, placebo-controlled trial enrolled 47 patients across 15 U.S. sites, and was designed to assess the safety and efficacy of a once-daily 5 mg dose of elobixibat over 16 weeks in adult patients with biopsy-confirmed NASH or a diagnosis of suspected NAFLD or NASH based on metabolic syndrome definitions. The primary endpoint was change from baseline in LDL-C. Secondary endpoints included change in liver fat by imaging, and in ALT and aspartate aminotransferase levels. Exploratory endpoints included measures of glucose and insulin homeostasis, which are biomarkers for inflammation and fibrosis.
“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,” said Ron Cooper, president and CEO of Albireo. “Our main focus continues to be on odevixibat in rare pediatric liver diseases and we look forward to our Phase 3 topline data in the coming weeks.”
Albireo is focused and remains on track with several milestones for the remainder of 2020, including topline results from the PEDFIC 1 pivotal Phase 3 trial of odevixibat in progressive familial intrahepatic cholestasis (PFIC) in the coming weeks, potential regulatory approval, issuance of a rare pediatric disease priority review voucher and odevixibat launch anticipated in the second half of 2021. Other anticipated events include initiation of a pivotal Phase 3 trial of odevixibat in Alagille syndrome by the end of 2020, and continued enrollment of patients in the BOLD pivotal Phase 3 trial of odevixibat in biliary atresia. Albireo also continues to progress development of a new preclinical candidate and expects to complete IND-enabling studies this year.
Elobixibat is a first-in-class, once-daily, oral ileal bile acid transporter (IBAT) inhibitor and is approved in Japan for the treatment of patients with chronic constipation (excluding constipation caused by organic disease). It is marketed and sold in Japan under the trade name GOOFICE.