In the market for treatments for gout, a condition in which uric acid, a waste product, builds up in the body, causing swollen joints and severe pain, signs of change are emerging. Until now, drugs that block uric acid production have been mainly used, but new treatments that promote uric acid excretion or address the limits of existing drugs are being developed in succession.
According to the industry on the 17th, interest is focusing on a potential shake-up of Korea's gout drug market after JW Pharmaceutical confirmed efficacy in global phase 3 trials of the uric acid excretion promoter "Epaminurad."
◇ Existing treatments focus on "inhibiting uric acid production"
Gout is a disease in which, as the concentration of uric acid in the blood rises, uric acid crystals accumulate in the joints or surrounding tissue, causing inflammation and severe pain. It is characterized by having no particular symptoms most of the time, with severe gout attacks occurring periodically.
In the past it was regarded as a condition common among middle-aged and older men, but recently, due to changes in diet, alcohol consumption, and an increase in obesity, the number of younger patients and women has risen. In particular, gout often appears alongside metabolic diseases such as obesity, hypertension, and hyperlipidemia, and is known to be associated with cardiovascular risk.
In Korea's current gout drug market, "Febuxostat," a uric acid production inhibitor developed by Japan's Teijin, leads the way. It works by inhibiting xanthine oxidase, an enzyme involved in uric acid production, thereby lowering blood uric acid levels. In addition, "Allopurinol," which inhibits uric acid production, and "Benzbromarone," which promotes uric acid excretion, are used.
However, treatments that directly promote uric acid excretion carried significant concerns about side effects. Benzbromarone, developed in the 1970s, failed to clear the U.S. Food and Drug Administration (FDA) approval bar after deaths were reported due to side effects such as hepatotoxicity. Although most gout patients are known to have elevated blood uric acid because the kidneys fail to properly excrete it, in Korea, because of these limits, treatments that reduce uric acid production have mainly been used.
◇ JW Pharmaceutical takes on challenge with a new "uric acid excretion–promoting" drug
Korean drugmakers are accelerating the development of gout treatments with new mechanisms that excrete uric acid, targeting the limits of existing therapies.
JW Pharmaceutical's gout drug candidate "Epaminurad" recently confirmed efficacy in global phase 3 trials. The company plans to submit a new drug application (NDA) aiming for domestic approval next year.
Epaminurad selectively inhibits urate transporter 1 (URAT1) in the renal proximal tubules. It prevents uric acid from being reabsorbed in the kidney, increasing excretion through urine.
In the global phase 3 trial, Epaminurad showed superior efficacy in lowering blood uric acid compared with Febuxostat, the current standard therapy. An analysis of the primary efficacy endpoint, the "proportion of patients achieving serum uric acid less than 6 mg/dL in the last three measurements of the main study period," found that the Epaminurad 6 mg group was 50.0% (76 of 152), higher than 38.3% (59 of 154) in the Febuxostat 40 mg group.
Some Korean companies are developing new drugs with mechanisms different from existing treatments. SK Chemicals, the distributor of Febuxostat, received approval from the Ministery of Food and Drug Safety last year for a phase 3 clinical trial plan for the gout treatment "SID2406," which is underway.
LG Chem, which had been developing the fastest, halted the global trial of the uric acid production inhibitor "Tigulixostat" in March due to commercial viability issues. However, development in China continues through its Chinese partner Innovent Biologics. A trial is underway to confirm superiority compared with Allopurinol.
◇ Global market also sees competition for "new gout drugs"
Overseas, competition to develop gout treatments with new mechanisms is also continuing.
"NASP," developed by Sweden's SOBI, is a treatment that prevents gout symptoms by breaking down uric acid in the blood to lower levels. It was expected to become the first treatment for chronic refractory gout, but in June it received a complete response letter (CRL) from the FDA requesting quality and manufacturing (CMC) supplements.
In the United States, a representative treatment approved by the FDA for gout patients who do not respond to existing therapy is Amgen's "Krystexxa."
Arthrosi Therapeutics in the United States is developing "AR882," which has a new uric acid excretion–promoting mechanism. AR882 selectively inhibits a renal urate transporter to block uric acid reabsorption and increase excretion through urine, and is currently in global phase 3 trials. It has also received fast-track designation from the FDA.
In the industry, given that existing treatments have dominated the market for a long time, if gout drugs with new mechanisms prove efficacy and safety in clinical trials, the market landscape could change. In particular, the key to commercialization will be how much they can reduce side effects of existing excretion promoters, such as hepatotoxicity or urolithiasis, while promoting uric acid excretion.
An industry official said, "Because gout treatments are often taken long term, not only efficacy but also safety and dosing convenience are important," and added, "If treatments with new mechanisms demonstrate clear advantages over existing drugs, the choices for clinicians and patients could expand."