NASP Improves Outcomes in Uncontrolled Gout, With Puja Khanna, MD

Findings from a recent study on Nanoencapsulated Sirolimus Plus Pegadricase (NASP) treatment for uncontrolled gout show improved sUA levels, patient-reported outcomes, and health-related quality-of-life (HRQOL) in patients1.

The phase 3 DISSOLVE Trials investigated the effects of NASP, formerly SEL-212, a 2-component infusion therapy made up of nanoencapsulated siroliumus, aimed to reduce the formation of anitpegadricase antibodies and uricase, which is meant to lower sUA1,2.

“NASP has been shown to reduce the number of swollen and tender joints, and the health-related quality-of-life measures, maintained at a level of above 80% across the board, whether patients took the high-dose NASP or the low-dose NASP,” said Puja Khanna, MD, MPD, University of Michigan, in an interview with HCPLive at the American College of Rheumatology (ACR) Convergence 2025. “So at the end of the day, this drug is showing promise that patients who have not previously responded to the oral therapies, despite being on full doses, have hope that they can attain remission.”

The trial included patients with a history of symptomatic gout, defined as ≥ 3 gout flares within 18 months of screening, 1 or more tophus, or current gouty arthritis, inability to normalize sUA, and control symptoms with treatment, and 7 mg/dL or more of sUA.

After applying the eligibility criteria, patients were randomized in a 1:1:1 ratio to receive 6 treatments of high-dose NASP (0.15 mg/kg NAS; 0.2mg/kg P), low-dose NASP (010 mg/kg NAS; mg/kg P), or placebo on a 4-week basis. Patient-reported outcomes were measured by a 36-Item Short Form Health Survey physical component summary score and Health Assessment Questionnaire-Disability Index pain score.

The week 1 baseline for HD NASP (n = 42), LD NASP (n = 35), or placebo (n = 67) (mean SD: 8.5 (1.4), 8.5 (1.3), and 8.7 (1.6) mg/dL compared to mean 1.1 (2.0), 0.5 (0.8), and 8.5 (2.0) mg/dL at week 24. For high-dose NASP, the means were reduced for sUA (-88%), tender joints (-74%), swollen joints (-90%), and pain score (-60%). For low-dose NASP, mean sUA reduced (-94%), tender joints (-92%), swollen joints (-90%), and pain score (-80%). For PBO, means were sUA, (-0.3%), tender joints (-40%), swollen joints (-54%), and pain score (-44%).

Further analysis of the results demonstrated significant improvement in uncontrolled gout symptoms in patients who received either a high or low dose of NASP. After the first dose of NASP, sUA levels were immediately reduced and remained ≤2.0 mg/dL. By the conclusion of the trial, there was a 2-fold reduction in the mean number of tender and swollen joints in the high-dose and low-dose NASP compared to PBO. The mean recorded patient outcome scores showed improvement (High-dose NASP, 5.9; Low-dose NASP, 9.7) and were 2-fold higher than the patients in the PBO cohort.

“The next steps would be to understand whether the six-month therapy is the end, or whether it needs to be continued for another six months. How many courses of NASP would a patient need? Because for every patient with uncontrolled gout, multiple flares, a massive amount of TOPHI deposits, it's not the same,” said Khanna about what she hopes to see in future research. “All of that data will have to be collected long-term before we can decide NASP is the drug of choice. Patients can have more options now. This space, unfortunately, has been very limited.”

References

1. Nanoencapsulated Sirolimus Plus Pegadricase Reduced Disease Burden in Patients With Uncontrolled Gout: Results From the Phase 3 DISSOLVE Trials - ACR Meeting Abstracts. ACR Meeting Abstracts. Published 2025. Accessed October 30, 2025. https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-reduced-disease-burden-in-patients-with-uncontrolled-gout-results-from-the-phase-3-dissolve-trials/

2. ‌Herbert, Khanna PP, Kivitz A, et al. The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTORTM) versus pegloticase for refractory gout. Rheumatology. Published online July 14, 2023. https://doi.org/10.1093/rheumatology/kead333