Promising Combination Treatment for Gout

Gout is the most common form of inflammatory arthritis in the U.S., affecting nearly 8.3 million people. The condition is caused by high serum uric acid (sUA) levels, which lead to the desposition of monosodium urate crystals in the body that accumulate around joints and other tissues. These deposits, called tophi, can cause debilitating flares and intense pain. Tophi occur in different parts of the body, including elbows, knees and cartilage around the ears. If left untreated, these harmful monosodium urate deposits in tissue can cause joint deformity. Patients with high sUA levels can also develop uric acid kidney stones.¹

Gout appears to be more prevalent in men (5.9%) than women (2%). Approximately 200,000 people in the U.S. suffer from uncontrolled gout, with sUA levels above 6 mg/dL despite treatment with urate-lowering, oral therapies. The risk of gout increases with age, with its frequency in individuals over the age of 80 being 30-fold higher than in individuals age 20–29 years-old. The risk of gout also increases with obesity and metabolic syndrome. Elevated sUA levels have also been associated with heart, vascular system, metabolic, kidney and joint diseases.

New Treatment

In September, the U.S. Food & Drug Administration (FDA) accepted the biologics license application for nano-encapsulated sirolimus with pegylated-adricase (NASP), formerly SEL-212, to treat uncontrolled gout. Previously, in May 2024, the FDA granted the treatment Fast Track designation, recognizing its potential to address a serious condition with high unmet need and limited treatment options.²

Tolerogenic NASP is a combination treatment being investigated to reduce sUA levels in patients with uncontrolled gout. Nano-encapsulated sirolimus diminishes anti-drug antibody formation in combination with pegylated-adricase (i.e., pegadricase; a uricase), which is used to reduce sUA levels. Anti-drug antibodies develop due to undesired biologic medicine immune responses that reduce medication effectiveness and tolerability. The effect of antidrug antibodies is often difficult to mitigate and can be seen in multiple therapeutic modalities and disease states that use biologic treatments, including patients with uncontrolled gout.

NASP is administered every four weeks as a sequential, two-component, infusion combination therapy.

The Data

This FDA application is based on findings from the DISSOLVE I and II clinical trials (NCT04513366; NCT04596540). Both studies met their primary end point of achieving and maintaining a reduction in sUA levels of less than 6 mg/dL for at least 80% of the time in up to six months.^3–5  

In the studies, the pooled response rates were 51% for patients who received high-dose NASP and 43% for patients who received low-dose NASP. The high-dose infusion consisted of 0.15 mg/kg of nano-encapsulated sirolimus and 0.2 mg/kg of pegadricase. Meanwhile, the low-dose infusion consisted of 0.10 mg/kg of nano-encapsulated sirolimus and 0.2 mg/kg of pegadricase.

Adverse effects included mild to moderate stomatitis and infusion reactions, with some serious adverse reactions. Adverse reactions occurred in 3.4% of the low-dose NASP group and 9.2% of patients in the high-dose NASP group compared with no placebo-treated patients.

The FDA has set a Prescription Drug User Fee Act, or target action date of June 27, 2026. In the meantime, we wait and see if the combination therapy receives FDA approval.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Ursani M. Patient blog: Understanding gout symptoms and treatment. American College of Rheumatology. 2023 Apr 27.
2. FDA accepts biologics license application for Sobi’s NASP for patients with uncontrolled gout [news release]. Sobi. 2025 Sep 10.
3. A study of SEL-212 in patients with gout refractory to conventional therapy (DISSOLVE I) [NCT04513366]. ClinicalTrials.gov. 2025 Sep 11.
4. A study of SEL-212 in patients with gout refractory to conventional therapy II (DISSOLVE II) [NCT04596540]. 2024 Feb 20.
5. Phase 3 DISSOLVE program of SEL-212 in chronic refractory gout meets primary endpoint [news release]. Sobi. 2023 Mar 21.