LIVZON Pharmaceutical's Novel siRNA Drug YJH-012 for Gout Receives IND Approval from China's NMPA, Offering Potential Once-Every-3-to-6-Months Dosing

Gout is a common and complex type of arthritis caused by hyperuricemia. In recent years, the prevalence of hyperuricemia has been increasing annually, with a significant trend toward younger onset, making it the second-largest metabolic disease after diabetes. Data shows: the global prevalence of hyperuricemia is 19.3%, with up to 1.561 billion patients, about 10% of whom will develop gout. In China, the prevalence of hyperuricemia is approximately 14%, affecting 188-296 million people, with over 15.52 million new cases each year; the prevalence of gout varies regionally, ranging from 1-3%.

Uric acid is primarily generated from dietary intake and the breakdown of purine compounds in the body, metabolized by the liver. Under normal circumstances, the production and excretion of uric acid in the human body are in a dynamic balance, with the saturation concentration of uric acid in the blood being 420 μmol/L. Once blood uric acid exceeds this value, it enters a state of hyperuricemia, leading to the formation of sodium urate crystals, which deposit in joints and surrounding soft tissues, renal tissues, and blood vessels, causing severe pain, chronic inflammation, and even multi-organ damage. Based on the progression of the disease, gout can be divided into four stages: asymptomatic hyperuricemia, acute gout attack, progressive gout (chronic gout), and gouty nephropathy (severe complications).

Facing such a large patient population and severe disease impact, the current treatment options for gout are relatively limited and challenging. Acute phase treatments (such as nonsteroidal anti-inflammatory drugs, colchicine, corticosteroids) mainly alleviate pain but do not address the root cause. Chronic gout is the result of long-term, uncontrolled significant elevation of blood uric acid levels. First-line treatment drugs (such as uric acid production inhibitors, uric acid excretion enhancers, and uric acid degradation promoters) can reduce uric acid but face issues like low target achievement rates and side effects (e.g., hepatotoxicity, nephrotoxicity, severe allergic reactions). Since uric acid itself plays an important physiological role (e.g., antioxidant), medications must precisely regulate its concentration within a narrow safety window. Individual differences are significant, making it easy to disrupt the balance. There is an urgent need in the field of gout for more effective and safer innovative treatment approaches.

Livzon Medicine (with global rights) and YOUJIA BIO jointly developed a novel siRNA drug, YJH-012. Its Investigational New Drug (IND) application has been accepted by the National Medical Products Administration. Targeting gout with hyperuricemia, this drug differs from traditional medications that inhibit enzyme activity to block uric acid synthesis, achieving a breakthrough mechanism for long-term suppression of uric acid production at the genetic level. It is expected to provide a longer-lasting, safer, and more thorough solution for clinical use.

• Mechanism Breakthrough:The core mechanism of the drug is to utilize small interfering RNA (siRNA) technology, delivering chemically modified double-stranded molecules precisely to the liver—the primary site of uric acid synthesis—through a specific liver-targeting delivery system, GalNAc. Inside hepatocytes, the siRNA molecules bind with the RNA-induced silencing complex (RISC). The helicase within RISC unwinds the siRNA duplex, releasing its guide strand. This guide strand accurately identifies and binds to the messenger RNA (mRNA) corresponding to the target protein, guiding the endonuclease within RISC to cleave and degrade it. The disrupted mRNA can no longer serve as a template for synthesizing the target protein, thereby significantly reducing the production of key pathogenic proteins at the source and blocking the uric acid production pathway.

  
  

• One-needle long-acting:Due to factors such as the strong stability of chemically modified siRNA, liver-targeted delivery constructing an intracellular sustained-release reservoir, and the long half-life of the RISC complex, a single administration of YJH-012 can achieve continuous uric acid reduction for 3-6 months. Preclinical validation: In cynomolgus monkey models, the uric acid-lowering effect lasted up to 180 days after a single dose (10 mg/Kg). Moreover, uric acid suppression increased steadily and was maintained long-term, avoiding the rapid drop in uric acid at the beginning of treatment that could lead to "crystal dissolution reaction" and trigger secondary gout. Compared with existing treatments, it demonstrates superior therapeutic potential.

  
  

• Safety Potential:Mechanism of action involves precise inhibition of target protein expression at the genetic level, with strong specificity and low off-target effects. In preclinical studies, no abnormal elevation of key purine metabolites such as hypoxanthine, IMP, AMP, and GMP was observed, nor were any liver-related pathological changes found, preliminarily indicating favorable safety characteristics.

  
  

YJH-012 is planned to initiate Phase I clinical research after approval, using an administration regimen of subcutaneous abdominal injections once every 3 or 6 months, to evaluate its safety and efficacy in humans. In the future, the potential of this drug in gout prevention and combination therapy with other uric acid-lowering drugs will also be explored, providing patients with better options.