Evopoint published Phase II clinical trial data of XNW3009, a new drug against gout

The prevalsence and incidence of hyperuricemia and gout are increasing year by year all over the world, highlighting an increasing trend in global drug market. However, there is a poor curative effect of relevant therapeutic agents although gout and hyperuricemia have become one of the common chronic diseases following the "three-hypers" gradually. In view of this clinical pain point globally, Evopoint independently developed XNW3009, a new small-molecule selective URAT1 inhibitor.

Dr. Zhanguo Li, director of the Peking University People's Hospital, who led the project, said that there are a surprisingly huge number of people who suffer from high uric acid in China at present, leading to a high incidence of gout, which require to be managed by using therapeutic agents with higher safety and efficacy clinically. According to the clinical trial data of XNW3009, it revealed a significant improvement in the efficacy and safety compared with the positive controls, suggesting that XNW3009 can be a 'Best in Class’ drug for the treatment of gout.

About XNW3009

XNW3009 Tablet is a new small-molecule selective URAT1 inhibitor with independent intellectual property rights owned by Evopoint Biosesciences Co., Ltd. It can significantly inhibit the activity of human uric acid transporter 1 (hURAT1), with its IC50 of >40 times lower than that of other URAT1 inhibitors of the same category (e.g., Benzbromarone and Lesinurad). Accordingly, XNW3009 exhibits a potential advantage that it can achieve better lowering effect of uric acid at very low doses.

XNW3009 Tablet is designed and developed based on unique pharmaceutical and chemical properties. Firstly, XNW3009 has relatively stable metabolism in hepatic cells, without intermediate products of metabolism related to hepatotoxicity that may occur when using Benzbromarone. In vitro hepatotoxicity test also showed that the hepatotoxicity of XNW3009 was significantly lower than that of Benzbromarone. Secondly, XNW3009 has expanded safety window of medication compared with other commercial products of the same category, which may effectively overcome or greatly reduce the risk of hepatotoxicity and nephrotoxicity of the proposed commercial products with the same target. Thirdly, XNW3009 has good pharmacokinetic properties, showing small individual variation, and no feeding effect or CYP enzyme induction. Its plasma concentration at the recommended dosage is far lower than the CYP enzyme/transporter inhibitory concentration.

Mr. Meijie Le, CEO of Evopoint, said that XNW3009 Tablet will be involved in a Phase III clinical trial in the near future. According to its Phase II clinical trial, the serum uric acid (sUA) concentration of >72% of the subjects in the 0.5mg dose group could be ≤360umol/L after each administration. While only 51.9% of the subjects in the control group giving Benzbromarone at 50mg could reach the same range of level. Therefore, XNW3009 Tablet at the test dosage showed an excellent lowering effect of uric acid compared with Benzbromarone. Moreover, it was safe and well tolerated, with mild adverse events of grade 1-2 in most cases, and no obvious side effects such as hepatotoxicity and nephrotoxicity. Besides, XNW3009 also revealed good pharmacokinetic and pharmacodynamic properties in clinical pharmacology. In general, patients with gout may have comorbidities of hypertension, hyperglycemia, hyperlipidemia, etc. Significantly, XNW3009 has no CYP enzyme induction, leading to a low risk of developing PK related drug-drug interactions, which is thus convenient for clinical use.

About gout and hyperuricemia

Evopoint will continue to make every effort to promote the clinical trials of XNW3009, and strive to accelerate product launch to benefit patients globally, so as to offer the majority of gout patients a new, safer and more effective therapeutic option. As a metabolic disease with serious harm, gout may prone to a protracted course of disease after repeated attacks, which is difficult to cure clinically.

Hyperuricemia is considered to be the key biochemical basis of gout, and about 5%~19% of patients with hyperuricemia may develop into gout. Moreover, hyperuricemia and gout are also independent risk factors for chronic kidney disease, hypertension, cardiovascular and cerebrovascular diseases, diabetes, etc. About 1/3 of patients with chronic gout have kidney damage (e.g., chronic gouty nephropathy, acute renal failure and urinary calculi). Furthermore, sUA level also exhibits an intimate association with cardiovascular complications, peripheral neuropathy, diabetes retinopathy, diabetes nephropathy and other organ impairment in patients with diabetes. It has been documented that every 60μmol/L increase in sUA may increase the relative risk of hypertension by 1.4 times, the risk of new-onset diabetes by 17%, the risk of renal diseases by 7%-11%, the risk of worsening renal function by 14%, the mortality risk of coronary heart disease by 12%, and the all-cause mortality risk of CKD patients by about 8%.

Generally, hyperuricemia is a metabolic condition caused by increasing production and/or decreasing excretion (in about 90% of hyperuricemia patients) of uric acid. Therefore, reducing sUA by increasing the excretion of uric acid may be an effective uric acid-reducing treatment. Urate transporter 1 (URAT1) is a major protein that regulates the re-absorption of uric acid. It is located in the proximal convoluted tubule of the kidney, which is responsible for the re-absorption of about 90% of uric acid in the kidney. URAT1 has been considered to be a new target for the treatment of hyperuricemia and gout in recent decades. The re-absorption of uric acid can be suppressed by inhibiting the activity of URAT1, so as to reduce the level of sUA.