A research group led by Assistant Professor Hisamu Hayashi of the University of Tokyo is targeting patients with progressive familial intrahepatic cholestasis type 2 (PFIC2), which is an intractable pediatric disease. Start a phase II study (doctor-led clinical trial) to confirm the efficacy and safety of NaPB).The clinical trial coordinator is Hiroki Kondo, a lecturer at Kinki University. This is the world's first drug development for PFIC2.
PFIC2 is designated as a chronic specific pediatric disease, and if left untreated, it is an intractable disease that progresses to liver failure in early childhood and leads to death.Currently, liver transplantation is the only treatment method, but due to problems such as a shortage of donors and a large physical and financial burden, the development of a drug-based treatment method is eagerly desired.
PFIC2 is caused by a mutation in a gene called BSEP.The research group found that in many PFIC2 patients, BSEP expression in the bile canaliculus flank of hepatic parenchymal cells was attenuated and BSEP function per hepatic parenchymal cell was reduced.Furthermore, it was found that NaPB, which is a therapeutic agent for urea cycle disorders, enhances the cell membrane expression level of BSEP.Therefore, based on the results of animal experiments and analysis of past data, a dose-escalation test of NaPB was conducted in PFIC2 patients, and the efficacy against PFIC2 was shown, and no side effects caused by the drug were observed.
Based on the above results, a doctor-led clinical trial is planned with the aim of obtaining regulatory approval for NaPB.Supported by the Future Medical Center, Future Medical Development Department, Osaka University Children's Hospital, and the National Center for Child Health and Development.In the clinical trial, the investigational drug will be administered to patients for 24 weeks, and its effectiveness will be evaluated based on changes in liver histology by liver biopsy. Six PFIC2018 patients are scheduled to participate in 3 facilities nationwide during the clinical trial period until March 6.It is expected that this clinical trial will greatly advance the development of drugs for intractable diseases through drug discovery research from universities.
