Intrahepatic Cholestasis of Pregnancy (ICP)

ICP is a liver disorder that occurs in pregnant women, usually presenting in the second and third trimester, which impairs the normal release of bile from liver cells and leads to impaired liver function. ICP can contribute to serious complications, particularly for the unborn child, including preterm labor and stillbirth. We estimate that each year there are approximately 40,000 cases of ICP in the United States and approximately 100,000 cases of ICP in Europe.

The underlying cause of ICP is not completely understood, but it is thought that a combination of genetic factors and altered expression of pregnancy hormones typically during the second and third trimesters contribute to the impaired liver function and bile flow characteristic of ICP. Also, some women have a genetic profile similar to that seen in other cholestatic liver diseases (e.g., PFIC, PSC). The disease can result in intense pruritus (itch), typically of the hands and feet. While cholestasis and the associated maternal pruritus typically resolve rapidly following birth, ICP can cause serious complications for the baby, including meconium-stained amniotic fluid, preterm birth, neonatal asphyxia and stillbirth. The rates of these events increase with increasing levels of maternal sBA.

Due to the lack of existing therapies which adequately address maternal pruritus and the potential for adverse outcomes for the baby, there remains a high unmet medical need for a safe and effective treatment option for ICP. There is no approved therapy for ICP in the United States, and while UDCA may be used off-label, large placebo-controlled studies suggest that UDCA may offer only minimal improvement for most patients. Elective early delivery (i.e., prior to full term) is often recommended as an option for high-risk pregnancies but bears the risk of long-term consequences for the child. We believe an ASBTi offers a substantial opportunity to address the maternal symptoms and associated fetal complications of ICP.

Intrahepatic Cholestasis of Pregnancy (ICP)

ICP is a liver disorder that occurs in pregnant women, often during the third trimester, which impairs the normal release of bile from liver cells and leads to impaired liver function. We estimate that each year there are approximately 40,000 cases of ICP in the United States and approximately 100,000 cases of ICP in Europe. ICP can contribute to serious complications, including preterm labor and stillbirth.

The underlying cause of ICP is not completely understood, but it is thought that the increase in pregnancy hormones during the second and third trimesters impairs liver function and the flow of bile. Also, some women have a genetic profile similar to that seen in PFIC. The disease can result in intense pruritus, typically of the hands and feet. It resolves rapidly following birth but can cause serious complications for childbirth, including meconium-stained amniotic fluid, preterm labor, neo-natal asphyxia and stillbirth. The rates of these events increase with increasing levels of maternal sBA. Induction of early delivery, i.e. before 36 gestational weeks, is an option for high risk pregnancies but bear the risk of long-term consequences for the child.

Due to the acute nature of the disease and potential for complications during pregnancy, there remains an unmet medical need for a safe and effective treatment option for ICP. There is no approved therapy for ICP in the United States, but UDCA is used off-label to decrease the concentration of harmful bile acids. However, reports suggest that UDCA offers minimal improvement for patients. Therefore, patients with ICP may benefit from treatment with an ASBTi.