1 INDICATIONS AND USAGE
1.1 Bile Acid Synthesis Disorders due to Single Enzyme Defects
CHOLBAM is indicated for the treatment of bile acid synthesis disorders due to single enzyme defects (SEDs) [See Clinical Trials(14.1)].
5 WARINIGS AND PRECAUTIONS
5.1 Exacerbation of Liver Impairment
Six patients with single enzyme defects underwent liver transplant, including four patients diagnosed with AKR1D1 deficiency, one with 3β-HSD deficiency, and one with CYP7A1 deficiency.
6 ADVERSE REACTIONS
- Deaths
In Tiral 1, among the 50 patients with SEDs, 5 patients aged 1 year or less died, which included three patients originally diagnosed with AKR1D1 deficiency, one with 3β-HSD deficiency and one with CYP7A1 deficiency.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
However, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintainbile acid homeostasis under normal physiologic conditions.
14 CLINICAL STUDIES
14.1 Bile Acid Synthesis Disorders due to Single Enzyme Defects
- Trials 1 and 2
Table 4: Response to CHOLBAM Treatment by Type of Single Enzyme Defect
|
Single Enzyme Defect |
Responders/Number Treated (%) |
|
3β-HSD |
22/37 (59%) |
|
AKR1D1 |
3/4 (75%) |
|
CTX |
2/2 (100%) |
|
AMACR |
1/1 (100%) |
|
CYP7A1 |
N/A* |
|
Smith-Lemli-Opitz |
N/A* |
*N/A indicates no evaluable patients in the defect subgroup represented.
Four patients in Trial 1 underwent liver transplant, including two patients diagnosed with AKR1D1 deficiency, one with 3β-HSD deficiency, and one with CYP7A1 deficiency and two patients in Trial 2, both with AKR1D1.
- Case Series
A published report of a case series described 15 pateints with SEDs; thirteen were diagnosed with 3beta-HSD deficiency and two with AKR1D1 deficiency by mass spectrometry and gene sequencing.
(2023.10.06 업데이트)