托匹司他 topiroxostat 汤森路透报告 Cortellis报告

topiroxostat

Table of Contents

Snapshot...........................................................................................................................................

2 Development Profile..........................................................................................................................

2 Development Status..........................................................................................................................

4 Chemical Structures..........................................................................................................................

5 Drug Names......................................................................................................................................

6 Clinical Trials..................................................................................................................................

6 Deals and Patents............................................................................................................................

7

13 Change History................................................................................................................................. Created:

18-Dec-2017

topiroxostat

SNAPSHOT

DEVELOPMENT PROFILE

SUMMARY

Fuji 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]. REGULATORY

In 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].

PREMARKETING

In 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].