Recently, the official website of the National Medical Products Administration (NMPA) announced that Chuangchun Genscience independently developed Class 1 innovative drug— Genakumab —has been officially approved for marketing.

It is intended for adult patients experiencing acute gouty arthritis attacks who are contraindicated for, intolerant to, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine, and who are not suitable for repeated use of corticosteroids.

With the three major clinical advantages of "long-term control, rapid and potent effect, and safety and reliability," Genakumab is expected to become the largest single product in the treatment of autoimmune diseases in China, meeting the huge market demand and safeguarding the health of a wide range of gout patients!

Gout is known as the "king of pain." According to the "2021 China Hyperuricemia and Gout Trend White Paper," there are approximately 177 million hyperuricemia patients in China, and more than 14.66 million patients suffer from gouty arthritis (GA), making it the second-largest metabolic disease after diabetes.

Although traditional treatment plans have been widely applied in clinical practice, nearly half of the patients still do not experience effective relief from pain and other symptoms, and about 60% of patients experience recurrent attacks within a year.

Particularly during the 3–6 months of uric acid-lowering therapy, about 12%–61% of patients may experience recurrent gout attacks. Recurrent gout can affect patients' adherence to uric acid-lowering treatment, leading to poor uric acid control and a vicious cycle that causes joint damage and may also affect key organs such as the heart and kidneys.

Research shows that within 60 days after a recurrent gout attack, the risk of heart attack or stroke can increase by 89%; within 30 days, the risk of venous thrombosis can rise by 131%; gout patients have a 4.61-fold increased risk of chronic kidney disease (CKD), which may rise up to 10 times with recurrent attacks. Moreover, the risk of developing end-stage renal disease also increases by 57% in gout patients with CKD.

Behind the repeated attacks of gout is the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in macrophages, which releases large amounts of interleukin-1β (IL-1β) and triggers an inflammatory cascade response. Both the acute and intercritical phases of gout are characterized by high levels of inflammation.

Persistent inflammation can significantly increase the cardiovascular and renal burden in patients, posing long-term and serious health risks. Therefore, long-term anti-inflammatory treatment is the cornerstone of gout therapy. At the same time, long-term anti-inflammatory treatment can reduce gout attacks, provide a better time window for achieving urate-lowering targets, and offer long-term benefits for the protection of target organs.

Traditional drugs carry many risks, making it difficult to achieve the desired therapeutic effect and are not conducive to long-term anti-inflammatory therapy for gout patients. Non-steroidal anti-inflammatory drugs may cause serious adverse effects such as gastrointestinal bleeding and cardiovascular disease; colchicine has a narrow therapeutic window, and improper use may lead to toxicity, while long-term use can cause gastrointestinal and hepatic-renal adverse reactions, significantly affecting quality of life.

It is expected that by 2030, the market size for gout medications in China will reach 10.8 billion yuan. Therefore, there is an urgent clinical need for innovative treatments that can control inflammation over the long term, reduce attack frequency, and be safer.

Genakumab works by precisely blocking IL-1β, which triggers gout-related inflammation. Clinical data show that a single dose of futuiazumab can quickly take effect, providing pain relief comparable to steroids within 6-72 hours, and reduces the risk of first recurrence by 87% within six months.

No serious drug-related adverse reactions have been observed. This approval is based on the results of a phase III clinical trial of Genakumab conducted in patients with gouty arthritis. This multicenter, randomized, double-blind, positive-control clinical trial enrolled a total of 313 patients with acute gout attacks, and the results showed:

• Primary endpoint: Improvement in 72-hour pain VAS score showed that the Fuxinqibai monoclonal antibody group was non-inferior to the compound betamethasone group, with a between-group difference of -3.32 mm (95% CI: -7.56, 0.91). The upper limit of the 95% confidence interval was 0.91 mm, which is less than the pre-specified non-inferiority margin of 10 mm, thus non-inferiority was established.

• Co-primary endpoint: Within 12 weeks after a single dose, the median time to first acute gout flare was not reached in the Genakumab group and was 45 days (95% CI: 28.00, 63.00) in the compound betamethasone group; the Genakumab group reduced the risk of first flare by 90% compared to the compound betamethasone group (HR=0.10, p<0.0001).

• Secondary endpoint: Within 24 weeks of administration, the Fuxinqibai group reduced the risk of first flare by 87% compared to the compound betamethasone group (HR=0.13, p<0.0001), with 85.3% of patients experiencing no recurrence, setting a best-in-class record among similar drugs and establishing its potential as a "Best-in-class" anti-inflammatory agent for gout.

• Safety: A total of 159 subjects (51.0%) experienced treatment-related adverse events, with 79 cases (50.6%) in the Genakumab group and 80 cases (51.3%) in the compound betamethasone group. No treatment-related serious adverse events were reported in the Genakumab group, while 3 patients in the compound betamethasone group reported treatment-related serious adverse events.

As the first IL-1β monoclonal antibody in China, the successful approval of Genakumab will quickly fill the gap in long-acting, anti-inflammatory, targeted therapy for gout in our country, bringing relief to a large number of patients suffering from repeated attacks of gouty arthritis.

>>About gouty arthritis

GA is a crystal-related arthritis caused by the deposition of monosodium urate in the joints. In recent years, its incidence has gradually increased and tends to affect younger individuals. GA can be divided into acute attack phase, intercritical phase, and chronic tophaceous gouty arthritis phase.

The typical manifestation of the acute attack phase is severe joint pain, which begins suddenly and progressively worsens. For patients with frequent attacks, or those who are contraindicated, intolerant, or unresponsive to NSAIDs and/or colchicine, and those unsuitable for repeated use of corticosteroids, there are currently no suitable treatment drugs available for clinical use in China. The introduction of Fuxinqibai monoclonal antibody will provide a breakthrough treatment option for patients who have long suffered from this disease.

>>Zvast Biotechnology - Animal Model of Gouty Arthritis

Modeling Method:

• Disinfect the right hind ankle joint of the rat with iodine.
• Bend the tibia and the sole of the foot to about 45°.
• Using a syringe, insert it at a 45° angle from the lateral side of the right hind ankle into the ankle joint cavity, ensuring the needle tip is within the joint cavity, and inject the solution.
• Inject 0.2 mL of sodium urate suspension into each rat, then withdraw the syringe (press with a cotton swab for a few seconds to prevent leakage).

24 hours after modeling, the rats' ankle joints on the modeled side were noticeably swollen. The average swelling rate in the model group reached 128.18%, while the average swelling rates in the allopurinol treatment group and benzbromarone treatment group were 127.67% and 114.88%, respectively, indicating successful modeling. At 96 hours after modeling, there was a significant difference between the model group and the benzbromarone treatment group (*P<0.05), whereas the difference between the model group and the allopurinol treatment group was not statistically significant.

Conclusion: Compared with allopurinol, benzbromarone has a certain therapeutic effect on acute gouty arthritis.

Reference：

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