Nanoencapsulated sirolimus plus pegadricase well tolerated with sustained efficacy over time in patients with uncontrolled gout, post hoc analysis finds
Presenter: Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, PA
Nanoencapsulated sirolimus plus pegadricase (NASP) demonstrates long term efficacy and safety in patients with uncontrolled gout: results from the 24-week double-blind extension of the phase 3 DISSOLVE I Study. Abstract 1123. Presented October 27, 2025.
Nanoencapsulated sirolimus plus pegadricase (NASP) provided sustained improvements in key clinical manifestations of uncontrolled gout, according to a post hoc analysis of a phase 3 study presented at ACR Convergence 2025.
Patients with uncontrolled gout had sustained reductions in serum uric acid and decreased gout flares through 48 weeks of treatment, according to results from the double-blind extension of the DISSOLVE I study.
At the end of the extension phase, more than 92% of patients on low-dose NASP and 100% on high-dose NASP were free of flares, the data show.
Previous data from DISSOLVE I showed results at week 24.
“The 48-week data continues to show the efficacy of NASP, and shows no new safety concerns,” said presenter Alan Kivitz, MD, of Altoona Center for Clinical Research in Duncansville, PA, in an interview.
Treatment with NASP was generally well tolerated in the post hoc analysis, and discontinuation rates in the extension phase were low.
“Flares continue to decline on a cumulative basis throughout the 48 weeks of treatment, and uric acid control does not wane with the additional 24 weeks of treatment,” Dr. Kivitz said in the interview.
“The data support the continuous efficacy of lowering uric acid and reducing flares with no new safety signals through 48 weeks of treatment with NASP,” he added.
Uncontrolled gout, which occurs when serum uric acid levels remain high despite treatment with oral urate-lowering agents, can result in progressively painful gout flares, Dr. Kivitz and co-authors noted in their study abstract.
NASP (formerly SEL-212) is a novel investigational therapy delivered every 4 weeks as a sequential, two-component infusion consisting of targeted nanoencapsulated sirolimus plus pegadricase, a pegylated uricase.
In the phase 3 DISSOLVE I study, patients were randomized to receive either high-dose NASP, low-dose NASP, or placebo every 4 weeks for 24 weeks. Following this main study period, patients could enter a double-blind extension for another 24 weeks.
At ACR Convergence, Dr. Kivitz and colleagues reported outcomes through 48 weeks in patients from the DISSOLVE I study who had received 6 doses of NASP or placebo during the main study period. They reported a total of 38 patients who received high-dose NASP, 37 who received low-dose NASP, and 37 who received placebo.
Results of the post hoc analysis showed that serum uric acid levels dropped after the first dose of NASP and stayed low through week 48.
Immediately after the first dose, the mean serum uric acid level dropped from 8.4 mg/dL to 0.2 mg/dL in the high-dose NASP group, and from 8.7 mg/dL to 0.2 mg/dL in the low-dose NASP group. By contrast, in the placebo group the level remained stable at 8.3 mg/dL before the first dose and 8.2 mg/dL after.
At week 4, the end of the first treatment period, the mean serum uric acid level was 1.0 mg/dL in the high-dose NASP group, 0.2 mg/dL in the low-dose NASP group, and 8.4 mg/dL in the placebo group.
Uric acid levels remained low throughout NASP treatment, according to the investigators. By week 48, the mean serum uric acid level was 2.4 mg/dL in the high-dose NASP group, 1.3 mg/dL in the low-dose group, and 8.1 mg/dL in the placebo group.
The investigators also reported on the proportion of patients with gout flares, which decreased with NASP treatment over the study period.
In the high-dose NASP group, flares occurred in 3 (15.8%) of 19 patients in weeks 1 through 4, 1 (5.3%) of 19 patients in weeks 21 through 24, and 0 of 16 patients in weeks 45 through 48. Similarly, in the low-dose NASP group, flares occurred in 7 (43.8%) of 16 patients in weeks 1 through 4, 2 (12.5%) of 16 patients in weeks 21 through 24, and 1 (7.7%) of 13 patients in weeks 45 through 48.
By contrast, in the placebo group, flares occurred in 7 (28%) of 25 patients in weeks 1 through 4, remaining at 7 (28%) of 25 patients in weeks 21 through 24, and 5 (22.7%) of 22 patients in weeks 45 through 48.
No new safety signals were reported in the extension phase, the investigators reported. One patient in each group discontinued treatment due to meeting stopping rule criteria. Overall, no patients experienced an infusion reaction within 1 hour of treatment.
In general, infusion reactions with NASP are infrequent and manageable with standard supportive therapy, according to Herbert S. B. Baraf, MD, FACP, MACR, Clinical Professor of Medicine at George Washington University.
In a separate presentation at ACR Convergence, Dr. Baraf and co-investigators reported a 4.0% incidence of infusion reactions among patients receiving NASP in the phase 3 DISSOLVE I and II studies.
No patient required blood pressure or ventilatory support, resuscitative efforts, or hospitalization, Dr. Baraf reported.
“As pegadricase in earlier studies was highly immunogenic, this study reinforces the improved safety of the combination of nanoencapsulated sirolimus followed by pegadricase,” Dr. Baraf said in an interview.
Disclosures
Alan Kivitz, MD, reported disclosures related to AbbVie/Abbott, Amgen, Coval, EcoR1, Eli Lilly, Fresenius Kabi, Genzyme, Gilead, GlaxoSmithKline (GSK), Grünenthal, Halia, Horizon, Innovaderm, Janssen, Novartis, Pacira, Pfizer, Prime, Princeton Biopartners, Prometheus, Sanofi-Regeneron, Santa Ana Bio Inc, Selecta, SynAct, Takeda, UCB, and XBiotech.
References
Kivitz A, Singhal A, Patel A, Azeem R, Peace B, Desai B, Baraf H. Nanoencapsulated sirolimus plus pegadricase (NASP) demonstrates long term efficacy and safety in patients with uncontrolled gout: results from the 24-week double-blind extension of the phase 3 DISSOLVE I Study [abstract]. Arthritis Rheumatol 2025; 77(suppl 9). https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-nasp-demonstrates-long-term-efficacy-and-safety-in-patients-with-uncontrolled-gout-results-from-the-24-week-double-blind-extension-of-the-phase-3-dissolv/. Accessed October 27, 2025.
Baraf H, Sulich AJ, Valenzuela GJ, et al. Characterization of infusion reactions within 1 hour of treatment with nanoencapsulated sirolimus plus pegadricase: pooled results from the phase 3 DISSOLVE I and DISSOLVE II trials [abstract]. Arthritis Rheumatol 2025; 77(suppl 9). https://acrabstracts.org/abstract/characterization-of-infusion-reactions-within-1-hour-of-treatment-with-nanoencapsulated-sirolimus-plus-pegadricase-pooled-results-from-the-phase-3-dissolve-i-and-dissolve-ii-trials/. Accessed October 27, 2025.
Dalbeth N, Choi HK, Joosten LAB, et al. Gout. Nat Rev Dis Primers 2019; 5(1):69. doi:10.1038/s41572-019-0115-y