武田薬品工業株式会社
Takeda (TSE:4502/NYSE:TAK) today announced that the Japanese Ministry of Health, Labour and Welfare has approved "LIVMARLI® Oral Solution 10 mg/mL (LIVMARLI)" for the treatment of pruritus associated with cholestasis in Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC).
LIVMARLI was developed by Mirum Pharmaceuticals, Inc. (Mirium). In September 2021, Takeda entered into a licensing agreement for the exclusive development and marketing rights of LIVMARLI in Japan. LIVMARLI is approved in more than 40 countries for ALGS and more than 30 countries for PFIC including US and Europe.
ALGS is a rare genetic disorder that causes cholestasis, ultimately leading to progressive liver dysfunction. PFIC is a rare genetic disorder that leads to progressive liver disease, caused by the reduction of the ability of liver cells to produce bile and the buildup of bile in the liver cells. Both are designated as "specified pediatric chronic diseases" or "designated intractable diseases" in Japan.
The approval is based on the results of Phase III clinical trials in patients with ALGSS (TAK-625-3001, NCT05543174) and in patients with PFIC (TAK-625-3002, NCT05543187 ) conducted in Japan as well as multiple clinical trials conducted overseas.
"Alagille syndrome and progressive familial intrahepatic cholestasis are diseases often diagnosed in early childhood,” said Yasushi Kajii, R&D Japan Region Head. “Severe itching associated with cholestasis can lead to nighttime insomnia and reduced quality of life for patients and their caregivers. We hope that LIVMARLI will be a new treatment option in Japan for pruritus associated with cholestasis"
ALGS is a rare genetic disorder characterized by a reduction in interlobular bile ducts, which eventually leads to biliary stasis and progressive liver dysfunction. The estimated incidence is about 1 in 30,0001 people, and a national survey has put the figure at around 200-300 patients in Japan.2 ALGS can affect multiple organs, including the liver, heart, kidneys and central nervous system.3 Reports indicate that between 60% and 75% of ALGS patients require liver transplantation before reaching adulthood.4 Symptoms include jaundice, xanthomas and severe pruritus. The pruritus experienced by ALGS patients is the most severe seen among the chronic liver diseases, and most cases occur before the third year of life.5
PFIC is a rare genetic disorder that impairs bile secretion from liver cells, causing an accumulation of bile in the liver cells and progressive liver disease. Symptoms typically appear in infancy and include severe pruritus, jaundice, impairment of growth and liver dysfunction. In the U.S. and Europe, estimates indicate that one in 50,000 to 100,000 newborns is affected by PFIC6. PFIC is recognized as a chronic paediatric disease in Japan, but only about 2 to 8 new cases7 are registered annually with the Japan Children’s Research Institute for Chronic Untreatable Diseases. PFIC has been reported to have multiple subtypes based on the gene responsible for the condition, and all subtypes share the common features of bile secretion impairment and progressive liver disease.
LIVMARLI is an ileal bile acid transporter (IBAT) inhibitor suitable for oral administration and approved by the U.S. Food and Drug Administration (FDA) for the treatment of pruritus associated with cholestasis in patients with ALGS and PFIC. Moreover, it is approved in Europe for the treatment of cholestatic pruritus in patients with ALGS and PFIC. LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC2 (a subtype of PFIC) in the U.S. and Orphan Drug designation for ALGS and PFIC in the U.S. and Europe. In Japan, the Ministry of Health, Labour and Welfare granted Orphan Drug designation for the expected indications of ALGS and PFIC on December 16, 2022.
LIVMARLI Product Overview in Japan
| Product name | LIVMARLI® Oral Solution 10 mg/mL |
| Generic name | Malarixibat chloride |
| Indications | Pruritus associated with cholestasis of the following diseases -Alagille Syndrome -Progressive Familial Intrahepatic Cholestasis |
| Dosage and Administration | 〈Alagille Syndrome〉 The usual dosage is 200 μg/kg of malarixibat chloride administered orally once daily before a meal. After 1 week, increase to 400 μg/kg once daily. 〈Progressive Familial Intrahepatic Cholestasis〉 The usual dosage is 300 μg/kg of malarixibat chloride administered orally once daily before a meal. After 1 week, increase the dose to 300 μg/kg twice daily. After 1 week, increase the dose to 600 μg/kg twice daily. |
Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CTEXLI™ (chenodiol) tablets.
LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients 12 months of age and older; in Europe, it is approved for patients with PFIC three months of age and older.
For more information about Mirum, please visit the company's website or follow them on Facebook, LinkedIn, Instagram and Twitter.
We believe that Gastroenterology (GI) and liver diseases are not just life-disrupting conditions, but diseases that can impact a patient’s quality of life. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With over 35 years of experience in gastroenterology, Takeda has made significant strides in addressing GI patient needs with treatments for inflammatory bowel disease (IBD), acid-related diseases, short bowel syndrome (SBS), and motility disorders. We are making significant strides toward closing the gap on new areas of unmet needs for patients who have celiac disease, eosinophilic esophagitis, alpha-1 antitrypsin-associated liver disease and Crohn’s disease, among others. Together with researchers, patient groups and more, we are working to advance scientific research and clinical medicine in GI.
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.
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