Nanoencapsulated sirolimus plus pegadricase reduced disease burden in patients with uncontrolled gout, phase 3 study data show
Presenters:
Puja Khanna, MD, MPH, Division of Rheumatology, University of Michigan, Ann Arbor, MI
Angelo Gaffo, MD, Division of Rheumatology and Clinical Immunology, University of Alabama, Birmingham, AL
Nanoencapsulated sirolimus plus pegadricase reduced disease burden in patients with uncontrolled gout: results from the phase 3 DISSOLVE trials. Abstract 2587. Presented October 28, 2025.
Nanoencapsulated sirolimus plus pegadricase (NASP) demonstrates a reduction in gout flares: results from the phase 3 DISSOLVE studies. Abstract 2588. Presented October 28, 2025.
In patients with uncontrolled gout, nanoencapsulated sirolimus plus pegadricase (NASP) reduced disease burden and improved key disease manifestations, according to analyses of phase 3 trial data presented at ACR Convergence 2025.
The analyses of the DISSOLVE I and II randomized phase 3 studies of NASP show reductions in gout flares, fewer tender and swollen joints, reductions in serum uric acid levels, and improved health-related quality of life.
These presentations at the ACR meeting are among the latest analyses focused on NASP, a novel investigational therapy consisting of a uricase (pegadricase) administered sequentially with nanoencapsulated sirolimus to prevent immunogenicity.
“We have few options for these patients, and it is promising to have another agent,” said investigator Angelo Gaffo, MD, in an interview.
Currently, NASP is under review by the US Food and Drug Administration (FDA). In September, the FDA accepted a Biologics License Application for the novel therapy for the treatment of uncontrolled gout.
Disease burden findings
In one analysis of the DISSOLVE I AND II trials, investigator Puja Khanna, MD, MPH, reported that NASP treatment improved serum uric acid levels, joint exam findings, health-related quality of life outcomes, and more.
The analysis was focused on patients with uncontrolled gout who received 6 doses of high-dose NASP, low-dose NASP, or placebo, given every 4 weeks for 24 weeks.
These findings highlight meaningful reductions in disease burden and clinical manifestations of uncontrolled gout in NASP-treated patients, according to Dr. Khanna.
Serum uric acid declined substantially with NASP treatment, according to Dr. Khanna's report.
Serum uric acid levels dropped from baseline to the last treatment period by 88% in the high-dose NASP group and 94% in the low-dose NASP group. By comparison, they dropped by only 0.3% in the placebo group.
In an interview, Dr. Khanna said these findings suggest that NASP can have a noteworthy impact, not only on health-related quality of life, but also on acute gout symptoms.
As such, NASP may help address unmet treatment needs, she said, particularly as outcomes with currently available gout therapies are inadequate for many patients.
“It's not just your patient-reported outcomes, meaning how the patient is feeling,” said Dr. Khanna in the interview. “We are also seeing objective evidence that the tender and swollen joint counts went down. So I think what this particular therapy gives us is hope,”
Focus on gout flares
In a separate post hoc analysis, Dr. Gaffo and co-authors evaluated gout flares on NASP therapy versus placebo, also limited to those patients receiving 6 doses of NASP or placebo over the 24-week study period.
Over the course of the study, the proportion of patients with flares and number of flares decreased with NASP as compared with placebo, Dr. Gaffo reported at the ACR meeting.
In weeks 1 to 4 of the study period, the number of patients who had gout flares was similar, at 23.8% in the high-dose group, 28.6% in the low-dose group, and 20.9% in the placebo group.
However, during weeks 21 to 24 of the study, gout flares had decreased, affecting only 4.8% of the high-dose NASP group and 5.7% of the low-dose NASP group, compared with 22.4% of the placebo group.
According to Dr. Gaffo, these results demonstrate the potential of NASP to improve a key clinical outcome in pts with uncontrolled gout.
“It is expected to be more potent than conventional urate-lowering therapies, and an option for patients with uncontrolled gout despite first-line therapies,” he said.
The average number of gout flares was also lower in the treatment groups than in the placebo group in this post hoc analysis. During weeks 13 to 24, the average number of flares was 2.3 to 5.7 times lower in the NASP groups than in the placebo group.
Cumulative gout flare rates plateaued in the NASP groups between days 100 and 200, while in the placebo group, the cumulative gout flare rate continued to increase.
Disclosures
Puja Khanna, MD, MPH, reported disclosures related to Arthrosi, Olatec, Selecta Biosciences, and Sobi. Angelo Gaffo, MD, reported disclosures related to Atom, Avalo Therapeutics, PK Med, Scilex, and Sobi.
References
Gaffo A, Baraf H, Patel A, et al. Nanoencapsulated sirolimus plus pegadricase (NASP) demonstrates a reduction in gout flares: results from the phase 3 DISSOLVE studies [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-nasp-demonstrates-a-reduction-in-gout-flares-results-from-the-phase-3-dissolve-studies/. Accessed October 31, 2025.
Khanna P, Majjhoo A, Azeem R, Peace B, Desai B, Strand V. Nanoencapsulated sirolimus plus pegadricase reduced disease burden in patients with uncontrolled gout: results from the phase 3 DISSOLVE trials [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-reduced-disease-burden-in-patients-with-uncontrolled-gout-results-from-the-phase-3-dissolve-trials/. Accessed October 31, 2025.
Ernst D. Novel combo therapy under review for uncontrolled gout. Rheumatology Advisor September 16, 2025. https://www.rheumatologyadvisor.com/news/novel-combo-therapy-under-review-for-uncontrolled-gout/. Accessed October 31, 2025.