What is elobixibat?

What is Elobixibat?

Elobixibat is an oral ileal bile acid transporter (IBAT) inhibitor that blocks bile acid reabsorption in the terminal ileum, increasing fecal bile acid excretion and colonic water secretion to treat chronic constipation. 1, 2

Mechanism of Action

• Elobixibat selectively inhibits the ileal bile acid transporter (IBAT), preventing bile acid reabsorption in the terminal ileum 3
• This interruption of the enterohepatic circulation increases bile acid delivery to the colon, which stimulates colonic secretion and motility 4
• The drug is minimally absorbed systemically, acting locally in the gastrointestinal tract 2
• Elobixibat increases plasma C4 (7α-hydroxy-4-cholesten-3-one) levels, a marker of bile acid synthesis, and reduces serum LDL cholesterol 2, 4

Clinical Applications

Chronic Constipation

• Elobixibat is approved in Japan for chronic constipation at a standard dose of 10 mg once daily before breakfast 1, 3
• The drug demonstrates efficacy in patients with severe constipation (≤2 spontaneous bowel movements per week), with dose escalation to 15 mg available for more refractory cases 5
• Efficacy is maintained over 52 weeks of continuous treatment without tachyphylaxis 3, 5
• The drug works equally well in patients with or without constipation-predominant irritable bowel syndrome (IBS-C) 1

Severe or Refractory IBS-C

• The British Society of Gastroenterology guidelines identify elobixibat as having evidential support for severe or refractory IBS-C, though it remains under investigation for this indication 6
• The drug is being tested in IBS-C populations, with preliminary data suggesting benefit 6

Progressive Familial Intrahepatic Cholestasis (PFIC)

• As an IBAT inhibitor, elobixibat represents a class of drugs used for medical interruption of the enterohepatic circulation in genetic cholestatic liver diseases 6
• While odevixibat (another IBAT inhibitor) has FDA/EMA approval for PFIC, elobixibat has been tested successfully in chronic idiopathic constipation and is likely to undergo testing in IBS-C 6

Dosing and Administration

• Standard dose: 10 mg once daily before breakfast 1, 3
• Dose range: 5-15 mg once daily, with titration based on response 5
• Food effect: Taking elobixibat before breakfast is essential, as food consumption reduces systemic exposure by approximately 80% while increasing the therapeutic effect (elevated plasma C4 levels) 2
• Duration: Demonstrated safety and efficacy for up to 52 weeks of continuous use 3, 5

Safety Profile

• Common adverse events: Mild abdominal pain and diarrhea, both dose-related and generally mild 1, 2
• Serious adverse events: No serious or severe adverse events occurred in phase 2 and 3 trials 1
• Tolerability: Well tolerated at doses up to 20 mg once daily for 14 days 2
• Quality of life: Improves constipation-related quality of life scores regardless of gender, presence of IBS-C, or occurrence of side effects 5

Clinical Efficacy Data

• Primary endpoint: Elobixibat 10 mg significantly increased spontaneous bowel movements from baseline (5.7 ± 4.2 times per week vs. 2.6 ± 2.9 with placebo, P = 0.0005) 1
• Dose-response: Higher doses (15 mg) provide additional benefit in patients with more severe constipation 5
• Bile acid effects: Increases fecal total and primary bile acids while decreasing serum secondary bile acids 4
• Sustained efficacy: Ameliorating effects observed from week 1 and maintained through week 52 of treatment 3

Important Clinical Considerations

• Patients with chronic constipation demonstrate decreased fecal bile acid levels compared to healthy subjects despite comparable bile acid synthesis markers (C4), suggesting impaired bile acid delivery to the colon that elobixibat corrects 4
• The improvement in bowel movements correlates with increased plasma C4 levels (R² = 0.5929 at week 2), providing a potential biomarker for response 2
• Drug-drug interaction studies suggest elobixibat may have a clinically slight inhibitory effect on P-glycoprotein 3