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Cinova URAT1 new gout drug pivotal Phase II data announced, aiming at Best-in-class

 Last Update: 2022-02-20
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Globally, the prevalence and number of patients with hyperuricemia (HUA) and gout are increasing year by year, and the global drug market is also showing a growing trend
.

However, with gout and hyperuricemia increasingly becoming one of the common chronic diseases after the "three highs", the clinical efficacy of drugs is unsatisfactory.

Ten billion market size, gout drugs need to break through

Uric acid is a product of purine metabolism, and its sources mainly include nucleic acids decomposed by endogenous cellular metabolism, as well as the metabolism and decomposition of other purine compounds and purines in exogenous food
.

Under normal physiological conditions, the synthesis and excretion of uric acid are in a dynamic balance, most of which are processed and excreted by the kidneys, and some enter the intestinal tract to be decomposed by bacteria

Reference 1

Therefore, hyperuricemia and gout can be said to be two different stages in the development of a disease
.

There are multiple evidences that hyperuricemia and gout are independent risk factors for chronic kidney disease, hypertension, cardiovascular and cerebrovascular diseases, and diabetes, and are independent predictors of premature death

According to the "Guidelines for Diagnosis and Treatment of Hyperuricemia and Gout in China (2019 Edition)", if the blood uric acid level exceeds 420 μmol/L twice on different days, it is judged as hyperuricemia
.

According to data from Frost & Sullivan, the total number of patients with hyperuricemia and gout in the world will exceed 1.

With the continuous growth of global patients, the global drug market size also continues to increase accordingly
.

The global gout drugs market size grew from USD 2.

Global gout drug market size (Source: Frost & Sullivan)

Market size of gout drugs in China (Source: Frost & Sullivan)

XNW3009 data released, URAT1 set off again

Uric acid is a key factor in inducing hyperuricemia and gout.
Therefore, the strategy of anti-hyperuricemia drug development is mainly to reduce uric acid production or promote uric acid excretion
.

Urate transporter 1 (URAT1) is a major urate transporter involved in the reabsorption and excretion of uric acid by the kidneys
.

A member of the organic anion transporter (OAT) family, URAT1 has 12 predicted transmembrane domains and is predominantly expressed in the cytoplasm and luminal membranes of proximal tubule cells in fetal and adult renal cortex

Reference source: TAKAHASHI CLINIC

Therefore, URAT1 inhibitors, as a strategy to inhibit uric acid reabsorption, have attracted many global pharmaceutical companies, including well-known multinational pharmaceutical companies such as Merck, Novartis, and Labaz (Sanofi)
.

However, due to safety factors such as hepatotoxicity and nephrotoxicity, the clinical use of URAT1 inhibitors is limited and the market sales are not good, leading to the voluntary withdrawal of many products from the market due to commercial reasons

XNW3009 developed by Sinovate is a novel URAT1 inhibitor, which can significantly inhibit the activity of human uric acid transporter 1 (hURAT1)
.

XNW3009 has a unique medicinal design.
On the one hand, XNW3009 has better metabolic stability in hepatocytes, and there is no metabolites produced by benzbromarone to cause hepatotoxicity.
benzbromarone; secondly, XNW3009 shows a higher safety window compared to similar drugs on the market, effectively overcoming or greatly reducing the risk of liver and kidney toxicity of drugs with the same target on the market; third, XNW3009 has Good pharmacokinetic characteristics, small individual variation, no food effect, no CYP enzyme induction, clinically recommended dose of blood drug concentration is much lower than CYP enzyme/transporter inhibitory concentration, and the possibility of drug-drug interaction is small, for concomitant It is convenient for clinical use in people with hyperuricemia (with or without gout) with chronic diseases such as hypertension, hyperglycemia, and hyperlipidemia
.

In 2019, XNW3009 conducted the first clinical study in Australia; in March 2021, Sinovate announced that XNW3009 tablets can reduce uric acid in patients with hyperuricemia (with or without gout) on the drug clinical trial registration and information publicity platform A multicenter, randomized, double-blind, benzbromarone-controlled, parallel-group phase II clinical study of efficacy and safety
.

On January 23, 2022, Cinova announced the latest progress of XNW3009
.

According to the announcement, XNW3009 is about to enter Phase III clinical trials

As far as the currently published data is concerned, XNW3009 has better efficacy and safety advantages, and has the potential of Best-in-Class
.
First, the proportion of subjects with serum uric acid concentration ≤ 360umol/L at a dose of 0.
5 mg of XNW3009 exceeded 72%, which was significantly better than that of lexinnula alone (29.
9%) and the control drug benzbromarone (51.
9%).
proportion of patients
.
Secondly, from the perspective of the development and commercialization path of similar products of URAT1, safety is the main bottleneck.
XNW3009 did not show obvious liver and kidney toxicity and side effects in the phase II study of similar products, and the adverse events were mostly 1~2 grade mild adverse events with better safety tolerability
.

XNW3009 has progressed rapidly in less than 10 months from the time the first patient was enrolled (2021-03-31) to the disclosure of the clinical trial results
.
Efficient execution and rapid advancement give XNW3009 a speed advantage among similar products in China.
Now that it has entered the Phase III study, it is expected to win the first domestically listed URAT1
.
Most importantly, the security advantage makes XNW3009 stand out in the competition for commercialization
.

Focusing on Best-in-Class/First-in-Class, Sinoway's strategic plan

From the clinical development progress of XNW3009, it is not difficult to see the strategic plan and strategy of Sinovax
.

Founded by senior leaders in science, industry and investment, Sinovate aims to provide high-quality solutions for major unmet clinical needs worldwide, and is committed to creating leading targeted therapy, PROTAC and antibiotic platforms
.
Currently, there are 6 products in the pipeline in the clinical development stage, 1 product in the IND-Enabling stage, and 15 products in the preclinical stage, with disease areas covering metabolism, anti-infection and tumor
.
Sinovax has R&D institutions in Suzhou, Shanghai, Beijing, Boston and Australia, with the mission of benefiting human health
.

XNW3009 is one of the products that Cinova is strongly promoting in clinical practice.
Professor Li Zhanguo, a well-known international and domestic expert in the field of rheumatism and immunity, has been hired as one of the PIs
.
XNW3009 has the potential of Best-in-Class efficacy and safety, which will be of great significance for improving the clinical nursing quality of hyperuricemia and gout
.
In addition, XNW7201 is a clinical drug with First-in-Class potential in the field of oncology.
It is the first product to carry out Phase II clinical research among domestic drugs with the same target
.

In terms of production capacity, in 2020, Sinovate will complete the purchase of 30 mu of industrialized land in Suzhou Industrial Park, which will serve as the production and operation base for future innovative pharmaceutical preparations
.
After the project is completed, the annual output will be 20 million sterile freeze-dried powder for injection, 400 million tablets and 600 million capsules
.
Support the commercial production and supply of 2-3 sterile injection varieties and 4-6 oral solid varieties
.

In the capital market, SinoVay has completed financing of more than 2 billion in the 4 years since its establishment, which shows that the capital market has recognized its experience and product prospects
.
In 2022, Cigna will start its IPO filing, and sufficient cash flow will ensure the continuous advancement of Cigna's clinical research and the development of new products
.

Summarize

In today's innovative drug involution, Fast Follow is the clamor for the supremacy, "only fast is not broken" is still the goal pursued by some pharmaceutical companies
.
However, looking at the life rules and commercialization status of URAT1 inhibitor products, it may be difficult to gain a foothold in this field by just relying on "fastness"
.
Only by polishing products with significantly differentiated effectiveness or safety like Sinovay, can we truly achieve stability and long-term success
.

References

reference material reference material

[1] Research progress of hyperuricemia.
Journal of Yunnan Minzu University (Natural Science Edition), 2021, 30(2): 135

[2] Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (2019).
Chinese Journal of Endocrinology and Metabolism, 2020:36(1):1

[3]Geographical distribution of hyperuricemia in China: a comprehensive systematic review and meta-analysis.
Global Health Research and Policy, 2020, 5:52

[4] Guidelines for Diagnosis and Treatment of Gout and Hyperuricemia Combining Disease and Syndrome.
DOI: 10.
13288/j.
11-2166/r.
2021.
14.
018

[5] Research progress of drugs for the treatment of gout and hyperuricemia.
Drug Evaluation Research, 2021, 44(8): 1811

[6] Talking about the treatment of hyperuricemia from "Chinese Expert Consensus on Hyperuricemia and Gout Treatment".
Drug Evaluation, 2014, 11(1): 21-23

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