FDA Approves Therapy for Severe Itching in Patients with Rare Liver Disease - Drug Information Update

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FDA Center for Drug Evaluation and Research Division of Drug Information

FDA approves therapy for severe itching in patients with rare liver disease

FDA has approved Bylvay (odevixibat), the first treatment for pruritus (moderate to severe itching) in patients aged three months and older with progressive familial intrahepatic cholestasis (PFIC), a rare progressive liver disease that typically leads to liver failure.

In a healthy liver, cells drain bile acids into bile (a fluid that aids digestion), and the bile acid is removed from the liver. However, in patients with PFIC, liver cells are unable to drain bile acids into the bile, and these toxic substances build up in the liver. The exact cause of itching in patients with PFIC is unknown; however, it may be caused by increased levels of bile acids in the body and skin. Itching in patients with PFIC can be severe and can result in bleeding, excoriations (skin picking), scars, and discomfort that impacts daily activities and sleep.

PFIC usually appears within the first few months of a person’s life and affects an estimated 1-2 people per 100,000. There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations.

Bylvay is a reversible inhibitor of the ileal bile acid transporter (IBAT) and decreases the reabsorption of bile acids from the small intestines. Although the complete mechanism by which Bylvay improves itching in PFIC patients is unknown, it may involve slowing or stopping bile acid absorption by blocking  the IBAT. Bylvay may not be effective in PFIC type 2 patients with ABCB11 variants, resulting in non-functional or absent bile salt export pump protein-3 (BSEP3).

The effectiveness of Bylvay for treatment of severe itching in PFIC patients was evaluated in “Trial 1,” a 24-week, randomized, double-blind, placebo-controlled study enrolling 62 pediatric patients aged 6 months to 17 years with PFIC type 1 or type 2 and severe itching. Patients were randomized to receive a placebo or Bylvay, either 40 mcg/kg or 120 mcg/kg. Bylvay was administered once daily with a meal in the morning.

Given the patients’ young age, the primary endpoints for this study were patients’ scratching as observed by their caregiver twice daily. Scratching was assessed on a 5-point ordinal scale, with scores ranging from 0 (no scratching) to 4 (worst possible scratching). After the 24-week study, patients treated with Bylvay demonstrated a greater decrease in itching or scratching compared to patients receiving a placebo.

Adverse events included increases in liver enzymes and bilirubin in patients taking Bylvay. Liver test monitoring should occur periodically during treatment. Bylvay may affect absorption of fat-soluble vitamins such as A, D, E and K. Patients should be monitored for fat soluble vitamin deficiency while taking vitamin Bylvay. Diarrhea was commonly reported and required pausing treatment or ending treatment. Patients and caregivers also reported abdominal pain and vomiting as common side effects while taking Bylvay.

A second study, “Trial 2,” supported the assessment of safety for Bylvay. The 72-week, open-label, single-arm study enrolled 79 patients with PFIC type 1, 2, and 3 between the ages of 4 months to 25 years. Patients received 120 mcg/kg of Bylvay administered once daily. Adverse events were similar to those observed in “Trial 1.”

Bylvay received fast track review and orphan drug designations.

FDA granted approval of Bylvay to Albireo Pharma, Inc.