Alagille Syndrome (ALGS)

Alagille syndrome (ALGS) is a rare, life-threatening multisystem disease that presents in childhood with a range of clinical manifestations, including jaundice (yellowing of the skin), pruritus (itch), failure to thrive (impacted growth in height and weight), xanthomas (disfiguring cholesterol deposits under the skin), and progressive liver disease, all of which can lead to liver transplantation.

The cholestatic pruritus is the most severe of any liver disease, negatively impacting patients’ quality of life. ALGS can result in progressive liver disease with only 24% transplant-free survival at 18.5 years of age. The management of ALGS is challenging as there are no approved therapeutic options, and currently used off-label therapies fail to adequately control the disease.

Alagille Syndrome (ALGS)

ALGS is a rare genetic disorder in which bile ducts are abnormally narrow, malformed and reduced in number, which leads to bile accumulation in the liver and ultimately progressive liver disease. The estimated incidence of ALGS is one in every 30,000 to 50,000 births in the United States and Europe, and we estimate that there are approximately 9,000 patients with ALGS in the United States and approximately 14,000 in Europe. We believe the addressable patient population will be a subset of these patients.

In patients with ALGS, multiple organ systems may be affected by the mutation, including the liver, heart, kidneys and central nervous system. The accumulation of bile acids prevents the liver from working properly to eliminate waste from the bloodstream and leads to progressive liver disease that ultimately requires liver transplantation in 15% to 47% of patients. Signs and symptoms arising from liver damage in ALGS may include jaundice, pruritus and xanthomas. The pruritus experienced by patients with ALGS is among the most severe in any chronic liver disease and is present in most affected children by the third year of life. Intractable pruritus can be severe enough to be an indication for liver transplantation. In patients who do not receive a liver transplant, 75% have active scratching, with 32% having destruction of skin, bleeding or scarring. Children with ALGS experience a markedly impaired quality of life largely due to the intense pruritus and associated skin lesions and disruptions in sleep and mood. A study to assess the health-related quality of life in ALGS patients indicated a significant burden in physical, psychological and social health accompanies the disease.

There remains a substantial unmet medical need for therapeutic options for ALGS, as PEBD and liver transplantation are the only options available for these patients.