Bylvay (odevixibat) - 2 indications

• for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis; approved July of 2021 
•  the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille syndrome; approved June of 2023

General Information

Bylvay (odevixibat) is a potent, non-systemic ileal bile acid transport inhibitor (IBATi).

Bylavy is specifically indicated:

• for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC);
• the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille syndrome (ALGS)

Bylavy is supplied as capsules and pellets for oral administration. Bylavy oral pellets are intended for use by patients weighing less than 19.5 kilograms. Bylavy capsules are intended for use by patients weighing 19.5 kilograms or above. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Odevixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. Pruritus is a common symptom in patients with PFIC and ALGS; the pathophysiology of pruritus in patients with PFIC is not completely understood. Although the complete mechanism by which odevixibat improves pruritus in both PFIC and ALGS patients is unknown, it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids.

Side Effects

Adverse effects associated with the use of Bylavy for PFIC may include, but are not limited to, the following:

• liver test abnormalities
• diarrhea
• abdominal pain
• vomiting
• fat-soluble vitamin deficiency

• diarrhea
• abdominal pain
• hematoma
• decreased weight

Indication 1 - for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis

approved July of 2021 

The recommended dosage of Bylavy is 40 mcg/kg once daily in the morning with a meal. If there is no improvement in pruritus after 3 months, the dosage may be increased in 40 mcg/kg increments up to 120 mcg/kg once daily not to exceed a total daily dose of 6 mg.

The approval of Bylvay was supported by data from PEDFIC 1 and PEDFIC 2, the largest, global, Phase 3 trials ever conducted in PFIC. In PEDFIC1, a randomized, double-blind, placebo-controlled study, Bylvay met both its pruritus and serum bile acid primary endpoints and was well tolerated with very low incidence of diarrhea/frequent bowel movements (9.5% of treated patients vs. 5.0% of placebo patients). PEDFIC 2, a long-term, open-label Phase 3 extension study, reaffirmed Bylvay delivered sustained reductions in serum bile acids as well as improvements in pruritus assessments, growth and other markers of liver function in patients treated up to 48 weeks.

Indication 2-  the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille syndrome

approved June of 2023

The recommended dose of Bylvay for ALGS patients 12 months and older is 120 mcg/kg taken orally once daily.

The FDA approval for ALGS was based on the phase 3 ASSERT trial, a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and efficacy of 120 µg /kg/day Bylvay for 24 weeks in relieving pruritus in patients with ALGS with 32 sites across North America, Europe, Middle East, and Asia Pacific. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS. In the primary analysis, the study met the primary endpoint showing highly statistically significant improvement in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), compared to the placebo arm. More than 90% of patients were pruritus responders (≥ 1 point change at any time during 24 weeks). The study also met the key secondary endpoint showing a highly statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24 (compared to the placebo arm. Statistically significant improvements in multiple sleep parameters were observed as early as weeks 1-4 compared to patients on placebo with continued improvement through week 24.