托匹司他 topiroxostat 汤森路透报告 Cortellis报告

topiroxostatTable of ContentsSnapshot...........................................................................................................................................2 Development Profile..........................................................................................................................2 Development Status..........................................................................................................................4 Chemical Structures..........................................................................................................................5 Drug Names......................................................................................................................................6 Clinical Trials..................................................................................................................................6 Deals and Patents............................................................................................................................713 Change History................................................................................................................................. Created:18-Dec-2017topiroxostatSNAPSHOTDEVELOPMENT PROFILESUMMARYFuji Yakuhin, in collaboration with Sanwa Kagaku, has developed and launched topiroxostat (FYX-051; SK-0910; Uriadec; Topiloric), an oral xanthine oxidoreductase inhibitor, which inhibits production of uric acid, as a tablet formulation, for the potential treatment of gout and hyperuricemia [932681], [1068682], [1229008], [1445821]. The product was launched in Japan in September 2013. Sanwa Kagaku launched under the tradename 'Uriadec', and Fuji Yakuhin launched under the name 'Topiloric' [1445821], [1472556].The company is also developing the drug for the potential treatment of diabetic nephropathy and chronic kidney disease [1623871], [1915020]. In March 2015, a phase II trial for diabetic nephropathy was initiated in Japan [1623871]. In June 2012, Fuji Yakuhin was seeking to outlicense the drug outside Japan [1307635]. REGULATORYIn June 2012, an application for approval was filed in Japan for topiroxostat in hyperuricemia and gout [1305082]. In April 2013, the Pharmaceutical Affairs and Food Sanitation Council's First Committee on Drugs was to discuss the application at a meeting on April 26, 2013 [1407389]; at the meeting, the committee recommended approval [1414256]. In June 2013, the drug was approved in Japan. At that time, Sanwa Kagaku Kenkyusho was to launch 'Uriadec' after the NHI price listing, and Fuji Yakuhin was to launch the drug under the name 'Topiloric' [1445821].PREMARKETINGIn March 2017, an open, randomized, parallel trial (UMIN000026741; TARGET-UA) to examine the effect of intensive UA-lowering therapy in patients (expected n=370) with CKD and hyperuricemia was planned to be initiated in Japan in June 2017 [1915020].In November 2016, clinical data from a 24-week, multicenter, open-label, randomized trial (ETUDE; UMIN 000015403), which evaluated the anti-albuminuric effects of topiroxostat in hyperuremic patients with diabetic nephropathy were presented at ASN's Kidney Week 2016 in Chicago, IL. Patients (n = 80) were randomized (1:1) to receive either high or low doses of topiroxostat (160 or 40 mg daily). After 24 weeks of treatment urine albumin-to-creatinine ratio (UACR; primary endpoint) significantly decreased by 122 mg/gCr in the high dose group, while in the low dose group the decrease was by 122 mg/gCr which was not significant. Mild and significant lowering effects on eGFR and systolic and diastolic blood pressure were observed in patients receiving topiroxostat, with steadily reduced serum uric acid levels [1878379].In February 2010, a multicenter, open-label phase III trial (JapicCTI-101068), of topiroxostat, began in patients with hyperuricemia in Japan. At that time, the expected study completion date was March 2012. In December 2011, the study was completed [1151860].In February 2016, a prospective, parallel, randomized, controlled phase II study (UMIN000020939; Excite-UA) was expected to be initiated in Japan, in chronIc heart failure patients complicated with hyperericemia [1736015].In December 2014, a double-blind, placebo-controlled, randomized, parallel assignment, phase II study (NCT02327754; FY1004) called 'UPWARD' was planned to be initiated in Japan to assess the safety and efficacy of the drug on urinary albumin excretion in patients (expected n = 60) with early stage diabetic nephropathy and hyperuricemia with or without gout. At that time, the study was expected to complete in December 2016. In March 2015, the trial was initiated [1623871].By August 2008, data from a phase II trial in patients with hyperuricemia had shown that topiroxostat significantly and dose-dependently lowered uric acid levels compared with placebo [932681].Also in August 2008, data from a completed 12-week study were reported. In the trial, patients received 40 mg bid for the first 2 weeks, followed by 80, 120, or 160 mg of topiroxostat bid for 10 weeks. Results showed that the uric acid levels of patients decreased in a 'close -to-maximum' manner 4 weeks after treatment began. At week 12, the percentage decrease from baseline in serum uric acid levels were 30, 39 and 47% for 80, 120 and 160 mg, respectively. No severe adverse events were reported, and the overall incidence of adverse reactions were similar among different arms [932681].By August 2008, pharmacokinetic studies had shown that topiroxostat was rapidly absorbed, reached Tmax within 1 h, and was eliminated from the blood with a half life of 4 to 7 h [932681].In 2003, a phase I trial began in UK [932681]. By August 2008, safety data from a Japanese phase I study had confirmed the results of the earlier UK phase I trial [932681].OTHER STUDIESIn November 2016, a single arm, interventional, non-randomized, open, uncontrolled trial () was planned to be initiated in Japan in patients (expected n = 36) with hyperuricemic congestive heart failure patients to assess heart function. At that time, the trial was expected to start in January 2017 [1878533]. PRECLINICALIn November 2016, preclinical data were presented at ASN's Kidney Week 2016 in Chicago, IL. In mice fed with febuxostat-high (3 mg/kg) and topiroxostat-high (3 mg/kg) diet, serum creatinine levels, urinary L-type fatty acid binding protein, urinary 15-F2t-isoprostane levels and urinary angiotensinogen were significantly lower when compared with the adenine group [1876279].In November 2015, preclinical data were presented at ASN's Kidney Week 2015 in San Diego, CA. Topiroxostat decreased urinary albumin excretion in db/db mice in dose-dependent manner. Hypertrophy of glomerulus and proximal tubules were attenuated. Plasma XOR inhibitory activity by topiroxostat in db/db mice was more than 12-fold stronger when compared with other XOR inhibitors [1708364].In August 2006, preclinical data were reported. In the in vitro study, metabolism of topiroxostat generated four conjugates in rat, dog, monkey and human. Urinary profile showed that the metabolites were similar among these mammals. The paper also mentioned that topiroxostat reduced serum urate concentration in a dose-dependent manner, and was 30-fold more potent than that of allopurinol in rats [932685]. DEVELOPMENT STATUSCURRENT DEVELOPMENT STATUSHISTORICAL DEVELOPMENT STATUSCHEMICAL STRUCTURESDRUG NAMESCLINICAL TRIALSTrials by Phase and Condition StudiedTotal Trials by Phase and StatusPhase DefinitionsPhase 3 ClinicalIncludes Phase 3, Phase 3b, Phase 3a, Phase 2/3 (where enrolment count is 300 or over)Phase 2 ClinicalIncludes Phase 2, Phase 2a, Phase 2b, Phase 1/2 (where enrolment count is 100 or over), Phase 2/3 (where enrolment count is under 300 or not specified)Phase 1 ClinicalIncludes Phase 1, Phase 1a, Phase 1, Phase 1/2 (where enrolment count is under 100 or not specified), Phase 0DEALS AND PATENTSDEALSDeals by Parent Company Chart Deals by Parent Company TableDeals by Type Chart Deals by Type TablePATENTSPatents by Parent Company ChartPatents by Parent Company TableCHANGE HISTORY SUMMARYCHANGE HISTORY DETAIL。