BYLVAY 200 MCG ORAL CAPSULE (ODEVIXIBAT)

🧬 What is Bylvay?

Bylvay (odevixibat) is an oral capsule that may be used to treat itching (pruritus) caused by progressive familial intrahepatic cholestasis (PFIC; a genetic disorder) in adults and children 3 months of age and older. A limitation of use is that it may not be effective in PFIC2, a subtype of PFIC caused by mutations in the ABCB11 gene.

Bylvay may also be used to treat cholestatic pruritus in patients 12 months of age and older with Alagille syndrome (ALGS).

• Generic Name: Odevixibat

• Brand Name: Bylvay

• Mechanism: Selective, reversible inhibitor of the ileal bile acid transporter (IBAT), reducing reabsorption of bile acids in the gut—ideal for cholestatic liver diseases

🏥 Indications

1. Progressive Familial Intrahepatic Cholestasis (PFIC)

   • For pruritus in patients aged ≥ 3 months

2. Alagille Syndrome (ALGS)

   • For cholestatic pruritus in patients aged ≥ 12 months

Note: Bylvay may NOT be effective in PFIC type 2 patients lacking functional BSEP protein .

💊 Dosing & Administration

PFIC (≥ 3 months)

• Start: 40 mcg/kg once daily with breakfast

• If no response at 3 months: Increase by 40 mcg/kg increments up to 120 mcg/kg daily, not exceeding 6 mg/day

ALGS (≥ 12 months)

• Dose: 120 mcg/kg once daily with breakfast .

• Formulation: Pellets for <19.5 kg; capsules for ≥19.5 kg

• Administration: Swallow capsules whole; mix pellets with soft food. Avoid bile acid resins ±4 hours .

⚠️ Key Warnings & Monitoring

• Diarrhea & Dehydration: Monitor GI function; manage hydration .

• Liver Tests: Check baseline and periodically (AST/ALT, bilirubin)

• Fat-Soluble Vitamins (A, D, E, K): Monitor and supplement to prevent deficiencies .

• Other Issues: Watch for abdominal pain, vomiting, liver decompensation. Contraindicated in active hepatic decompensation events like ascites or variceal bleeding

⚕️ Safety & Adverse Effects

Common (≥10%):

• Diarrhea, vomiting, abdominal pain

• Elevated liver enzymes, fat-soluble vitamin deficiency, increased bilirubin, splenomegaly .

Less Common (1–10%):

• Cholelithiasis, dehydration, fractures, hematoma, weight loss .

Serious/Postmarketing:

• GI hemorrhage, liver transplant, subdural hemorrhage, epistaxis.

✅ Clinical Trial Results

• PFIC Phase III trials showed significant itch reduction and improved sleep quality compared to placebo .

• ALGS trials (ASSERT study) demonstrated rapid and durable improvements in pruritus and bile acids with low diarrhea rates .

🌍 Regulatory Status

• FDA-approved for PFIC in 2021 and ALGS in 2023.

• EMA-approved for PFIC in children ≥6 months .

🧾 Summary

Bylvay (odevixibat) is the first-in-class IBAT inhibitor for cholestatic itch in PFIC & Alagille syndrome. It offers a meaningful reduction in pruritus, has a defined pediatric dosing profile, and requires careful monitoring of GI function, liver health, and vitamin levels due to potential adverse effects.