[Edaily Reporter Minji Son ] JWPHARMACEUTICAL(001060)’s new gout drug candidate, “Efamynurad,” has demonstrated its competitiveness at the 6 mg dose—its primary dosage—in a multinational Phase 3 clinical trial. The fact that it demonstrated superiority in a direct comparison with febuxostat—which dominates the gout prescription market—and possesses a differentiated mechanism of action bodes well for its approval and market entry. However, the development strategy for higher doses remains a challenge for the future. Furthermore, given the active global development of gout treatments, a differentiated approach is required in terms of the target patient population and dosing strategy.

Accelerating Approval for the Main 6 mg Dosage… Exploring Follow-up Strategies for Higher Doses

According to JWPHARMACEUTICAL on the 13th, the company released the top-line results of the multinational Phase 3 clinical trial for Epa-minurad on the 11th. The clinical results confirmed statistical superiority, showing that the 6 mg dosage demonstrated a greater reduction in serum uric acid levels compared to febuxostat 40 mg, the current standard of care.

This trial was conducted at 52 institutions across five Asian countries—including South Korea, Taiwan, Thailand, Malaysia, and Singapore—and involved 612 patients with gout. The study compared 6 mg and 9 mg doses of efaminurad with 40 mg and 80 mg doses of febuxostat, respectively.

The primary efficacy endpoint was the proportion of patients whose serum uric acid levels remained below 6 mg/dL in the last three measurements during the 24-week study period. The target achievement rate in the 6 mg efaminurad group was 50.0%, higher than the 38.3% observed in the 40 mg febuxostat group.

This is significant because it demonstrates superiority by using febuxostat—which accounts for over 80% of the total gout market—as the active comparator. In effect, it confirms a clinical difference through a head-to-head comparison with the market leader.

However, results for the high-dose groups were mixed. The uric acid target achievement rate in the 9 mg efaminurad group was 59.6%, higher than that of the 6 mg group but lower than the 63.3% achieved by the 80 mg febuxostat group. The difference in response rates between the treatment groups was –3.99%; since the lower limit of the 95% confidence interval (-15.0%) was lower than the non-inferiority margin of -10%, non-inferiority was not demonstrated for the primary efficacy endpoint.

JWPHARMACEUTICAL plans to first submit the 6 mg dose of Efaminurad for domestic marketing authorization. The company aims to obtain domestic marketing authorization next year. A JWPHARMACEUTICAL official stated, “We plan to begin the marketing authorization process for the 6 mg dose,” adding, “For the 9 mg dose, we plan to conduct follow-up analysis of data—selecting cases among treated patients where Epaaminurad was more effective than existing high-dose products—to support potential additional approvals or commercialization.”

Targeting ‘Excretion’ Rather Than Inhibition of Uric Acid… Competitors with the Same Mechanism Also Picking Up Speed

A major distinguishing feature of efaminurad is that its mechanism of action differs from that of allopurinol and febuxostat, which currently dominate the domestic market. Allopurinol and febuxostat are “uric acid synthesis inhibitors” that block the production of uric acid in the body by inhibiting xanthine oxidase. In contrast, epaminurad is a “uric acid excretion enhancer” that promotes the excretion of uric acid from the body by inhibiting URAT1, the uric acid transporter responsible for its reabsorption in the kidneys.

JWPHARMACEUTICAL noted that while a significant number of gout patients fall into the “excretion-deficient” category—characterized by impaired uric acid excretion—prescriptions for existing uric acid excretion enhancers have been limited due to safety concerns regarding the liver and kidneys. Accordingly, the company’s strategy is to secure efficacy and safety by selectively inhibiting URAT1 and establish the drug as a “best-in-class” new treatment within its class.

However, since overseas competitors with the same mechanism of action have already entered the commercialization phase or are conducting late-stage global clinical trials, competition to secure market share is expected to intensify. A representative product is Dotinurad, a selective URAT1 inhibitor developed by Japan’s Fujifarm. Dotinurad was approved in Japan in 2020 and has since expanded its approval to countries such as China, Thailand, and the Philippines. In China, it received approval in 2024 and was launched in July of last year. Previously, in a Phase 3 clinical trial in China, Dotinurad demonstrated superiority, with a 24-week achievement rate of serum uric acid levels of 6 mg/dL or lower of 73.6% in the 4 mg dose group, compared to 38.1% in the 40 mg febuxostat group.

Posdeutinuhrad, which Swedish pharmaceutical company Sobi acquired through its takeover of Atsrosi Therapeutics, is also a selective URAT1 inhibitor. In the global Phase 3 REDUCE 2 clinical trial, both the low-dose and high-dose groups met the primary efficacy endpoint. At 6 months, the rate of achieving serum uric acid levels below 6 mg/dL was 56.6% in the 50 mg group and 69.2% in the 75 mg group, significantly exceeding the 8.1% rate in the placebo group.

Of course, it is difficult to directly compare response rates because efaminurad used febuxostat as an active comparator, whereas posdeutinuhrad (AR882) was a placebo-controlled trial. Nevertheless, the fact that posdeutinuhrad has broadened the options for follow-up development across multiple dose levels is a factor accelerating competition in the market. Results from Pozdeutinuhrad’s second Phase 3 clinical trial, REDUCE 1, are scheduled to be released in the second half of this year. Sobi plans to file for U.S. marketing approval next year.

Phase 3 Trial for Tigulixostat in China… Competition Heats Up for Severe Gout Treatments

Meanwhile, the development of gout

treatments

is proceeding actively, even among drugs with different mechanisms of action. First, Innovent, which holds the Chinese rights to LGCHEM,LTD’s tigulixostat, began dosing the first patient in a local Phase 3 clinical trial last March. Inovent is comparing Tigulixostat with Febuxostat in a trial involving 600 Chinese gout patients. The study will evaluate the rate of achieving uric acid targets at Week 24 and long-term safety over one year. As a result, Inovent may face future competition from Simcere Pharmaceuticals, which holds the development and commercialization rights for Epaminurad in the Chinese market.

There have also been cases where approval efforts have hit a roadblock. Sobi’s NASP, a treatment for refractory gout, is an infusion therapy targeting adult gout patients whose condition is not controlled by oral urate-lowering drugs. It involves sequential administration of pegadrikase, which breaks down uric acid, and nanoparticle-form sirolimus, which suppresses the production of anti-drug antibodies. However, approval was delayed after the company received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) last June regarding issues with manufacturing controls and contract manufacturing facilities. Sobi stated that no issues affecting the likelihood of approval were identified in terms of clinical efficacy or safety and plans to resubmit the application within 6 to 12 months.

In addition, SKCHEMICALS’ gout treatment “SID2406” is currently undergoing Phase 3 clinical trials in Korea, and pharmaceutical companies both domestically and internationally are continuing to compete in development, targeting different mechanisms of action and patient populations.

A bioindustry official stated, “While a significant number of gout patients have impaired uric acid excretion, prescriptions for existing uric acid excretion promoters have been limited due to safety concerns such as liver toxicity, leading to a tendency to primarily use uric acid synthesis inhibitors out of necessity,” adding, “If a treatment emerges that promotes uric acid excretion while ensuring safety, it could differentiate itself not only from existing standard therapies but also from competing drugs with the same mechanism of action and other drugs currently in development with different mechanisms.”

He continued, “Ultimately, the biggest challenge is demonstrating both efficacy and safety simultaneously, and securing dosage escalation options for patients who do not respond adequately to treatment will be the next step.”