On June 27, 2026, the FDA is expected to decide whether to approve NASP (nanoencapsulated sirolimus plus pegadricase, formerly SEL-212), a novel two-component sequential infusion therapy for the treatment of uncontrolled gout in adults. Developed by Sobi (Swedish Orphan Biovitrum), NASP addresses a persistent problem in biologic therapy: anti-drug antibody (ADA) formation that renders treatment ineffective. If approved, NASP would be the first therapy to pair a tolerogenic immunomodulator with a biologic enzyme specifically to prevent ADA-mediated treatment failure.
This preview is for rheumatology access teams, infusion center pharmacists, payer medical directors, and specialty pharmacy operators who need to understand NASP's mechanism, clinical evidence, competitive landscape, and access implications ahead of the PDUFA date.
What NASP is and how it works
NASP is an investigational every-4-week infusion therapy consisting of two components administered sequentially:
- Nanoencapsulated sirolimus (NAS): Tolerogenic nanoparticles containing sirolimus (rapamycin), an mTOR inhibitor. NAS is designed to selectively suppress the immune response that produces anti-drug antibodies against the pegylated uricase, without causing broad immunosuppression.
- Pegadricase: A pegylated uricase enzyme that catalyzes the oxidation of uric acid to allantoin, which is far more soluble and easily excreted. Pegadricase rapidly lowers serum uric acid (sUA) levels.
The key innovation is the use of nanoencapsulated sirolimus as a targeted immunomodulator to prevent the formation of anti-drug antibodies against pegadricase. ADAs are a well-documented problem with uricase therapies — they reduce drug efficacy and can cause infusion reactions. By pre-treating with NAS before each pegadricase infusion, NASP aims to sustain uricase activity over time.
Key parameters:
| Parameter | NASP |
|---|---|
| Generic | Nanoencapsulated sirolimus plus pegadricase (NASP, formerly SEL-212) |
| Brand | Not yet assigned |
| Drug class | Two-component sequential infusion: tolerogenic immunomodulator + pegylated uricase |
| Mechanism | NAS prevents ADA formation; pegadricase lowers serum uric acid |
| Route | Intravenous infusion (sequential, two-component) |
| Dosing | Every 4 weeks; high dose: 0.15 mg/kg NAS + 0.2 mg/kg pegadricase; low dose: 0.10 mg/kg NAS + 0.2 mg/kg pegadricase |
| Manufacturer | Sobi (Swedish Orphan Biovitrum; co-developed with Selecta Biosciences) |
| Application type | BLA |
| PDUFA date | June 27, 2026 |
| Proposed indication | Uncontrolled gout in adults |
| Clinical trials | DISSOLVE I (NCT04513366), DISSOLVE II (NCT04596540) |
Uncontrolled gout: the disease landscape
Uncontrolled gout (also called chronic refractory gout) is defined as serum uric acid persistently ≥6 mg/dL despite treatment with oral urate-lowering therapies (ULTs) such as xanthine oxidase inhibitors (allopurinol, febuxostat). It leads to:
- Recurrent, debilitating gout flares
- Tophus formation (urate crystal deposits in joints and soft tissue)
- Joint destruction and deformity
- Chronic pain and disability
- Comorbidity burden (chronic kidney disease, cardiovascular disease, metabolic syndrome)
An estimated 200,000 people in the United States have uncontrolled gout despite conventional therapy. Current treatment options beyond oral ULTs are limited. Krystexxa (pegloticase), the only approved pegylated uricase, is effective but is limited by high rates of ADA formation that reduce its durability.
The regulatory timeline
- Sobi submitted the Biologics License Application (BLA) for NASP in 2025
- The FDA accepted the BLA for review on September 10, 2025
- The FDA set a PDUFA target action date of June 27, 2026
- The BLA is supported by data from the phase 3 DISSOLVE I and DISSOLVE II trials
DISSOLVE I and II: phase 3 trial results
Trial design
Both DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540) were double-blind, placebo-controlled, randomized phase 3 studies evaluating the safety and efficacy of NASP in adults with uncontrolled gout.
- Design: Patients were randomized 1:1:1 to high-dose NASP, low-dose NASP, or placebo
- Dosing: Intravenous infusion every 28 days for up to 12 infusions
- Primary endpoint: Serum uric acid <6 mg/dL for ≥80% of the time during month 6 (treatment period 6, TP6)
Individual trial results
| Endpoint | DISSOLVE I: High-dose | DISSOLVE I: Low-dose | DISSOLVE I: Placebo | DISSOLVE II: High-dose | DISSOLVE II: Low-dose | DISSOLVE II: Placebo |
|---|---|---|---|---|---|---|
| Response rate (sUA <6 mg/dL ≥80% of TP6) | 56% (P<0.0001) | 48% (P<0.0001) | 4% | 47% (P=0.0002) | 41% (P=0.0015) | 12% |
Pooled results (DISSOLVE I and II)
| Endpoint | High-dose NASP | Low-dose NASP | Placebo |
|---|---|---|---|
| Pooled response rate | 51% | 43% | 8% |
| Risk difference vs. placebo (95% CI) | 43.0 (28.0, 58.0); P<0.0001 | 35.0 (21.0, 49.0); P<0.0001 | — |
| sUA reduction from baseline to last treatment period | 88% | 94% | 0.3% |
Both doses met the primary endpoint in both trials with statistically significant and clinically meaningful improvements over placebo. Across 48 weeks, NASP-treated patients showed a 96.3% reduction in cumulative sUA area under the curve versus placebo, as presented at NKF-SCM 2026.
Gout flare reduction
Gout flare data from pooled DISSOLVE I and II (presented at ACR Convergence 2025):
| Period | High-dose NASP | Low-dose NASP | Placebo |
|---|---|---|---|
| Weeks 1–4 | 23.8% | 28.6% | 20.9% |
| Weeks 21–24 | 4.8% | 5.7% | 22.4% |
| Extension weeks 45–48 | 0% | 7.7% | 22.7% |
Flare rates decreased dramatically over time with NASP treatment, while remaining persistent in the placebo group. By the extension phase, 100% of high-dose NASP patients and 92.3% of low-dose NASP patients were flare-free.
Additional clinical benefits
Presented at ACR Convergence 2025 and American Society of Nephrology Kidney Week 2024:
- Fewer tender and swollen joints
- Improvements in health-related quality of life
- Sustained sUA reductions over 48 weeks
- Efficacy maintained in patients with chronic kidney disease (CKD stage 3): high-dose response rate 40% and low-dose 50% vs. placebo
Safety
- NASP was generally well tolerated
- Stomatitis (mouth sores, related to sirolimus): occurred in 9.2% of high-dose patients, 3.4% of low-dose patients, and 0% of placebo patients — consistent with the known effects of mTOR inhibitors
- Infusion reactions: A greater number were reported with NASP vs. placebo, though reactions were generally mild and no hospitalizations were required
- No new safety signals in the extension phase
- Low discontinuation rates during long-term treatment
- The most common early adverse events were gout flares (expected during urate-lowering initiation)
- In the DISSOLVE I 6-month extension, 75% of patients who completed 6 months as responders continued to respond at month 12, supporting durability
Competitive positioning vs. Krystexxa
Krystexxa (pegloticase) is the only currently approved pegylated uricase for uncontrolled gout. Comparing NASP with Krystexxa:
| Dimension | NASP | Krystexxa (pegloticase) |
|---|---|---|
| Components | Two-component sequential infusion (NAS + pegadricase) | Single-agent pegylated uricase |
| ADA prevention strategy | Nanoencapsulated sirolimus (tolerogenic) | Methotrexate co-treatment (off-label; increasingly adopted) |
| Dosing frequency | Every 4 weeks | Every 2 weeks |
| Administration | IV infusion (sequential two-component) | IV infusion |
| Phase 3 response rate | 51% (high dose) | ~42% in pivotal trials (with methotrexate pre-treatment, response rates increase to ~60–70%) |
| Manufacturer | Sobi | Amgen (formerly Horizon Therapeutics) |
| FDA status | BLA under review, PDUFA June 27, 2026 | Approved 2010 for chronic refractory gout |
| Anti-drug antibody management | Built into the product (NAS component) | Requires separate methotrexate prescription (not in label) |
Key differentiators:
- Integrated ADA management: NASP is the first therapy to incorporate ADA prevention directly into the product design, rather than relying on off-label coadministration of methotrexate
- Less frequent dosing: Every 4 weeks vs. every 2 weeks for Krystexxa
- Novel mechanism: The tolerogenic nanoparticle approach could have applications beyond gout — any biologic therapy subject to ADA formation could potentially benefit from this platform
Access implications if approved
Administration logistics
NASP will require:
- Infusion center administration: Sequential two-component IV infusion every 4 weeks
- Pre-infusion assessment: Monitoring for infusion reactions (as with other uricase therapies)
- Coordination: The sequential nature of the two-component infusion adds complexity compared with single-agent infusions
- Buy-and-bill or specialty pharmacy: Depending on payer and benefit design (medical vs. pharmacy benefit)
Medical benefit vs. pharmacy benefit
As an infused biologic, NASP will likely fall under the medical benefit on most commercial plans, which means:
- J-code assignment will be needed for claims processing (may take time post-approval)
- Buy-and-bill economics for rheumatology practices and infusion centers
- Interim billing risk if J-code assignment is delayed
- Prior authorization under medical benefit pathways (often slower and less standardized than pharmacy PA)
Prior authorization expectations
If approved, payers will likely require:
- Confirmed uncontrolled gout: Documented sUA ≥6 mg/dL despite oral ULT therapy
- Prior therapy: Failure, contraindication, or intolerance to xanthine oxidase inhibitors (allopurinol, febuxostat)
- Specialist prescriber: Rheumatologist or other qualified specialist
- Ongoing monitoring: Periodic sUA measurement to confirm response
- Krystexxa history: Some payers may require prior Krystexxa trial or documentation of why Krystexxa is not appropriate
Pricing considerations
- Krystexxa's wholesale acquisition cost is approximately $5,000–$7,000 per infusion (every 2 weeks), or roughly $130,000–$180,000 annually
- NASP pricing has not been announced; Sobi will need to price competitively, particularly given the less frequent dosing (every 4 weeks vs. every 2 weeks)
- Payers will evaluate cost-per-responder given the different response rates
What to watch
- FDA decision: June 27, 2026 PDUFA date; watch for approval, CRL, or extension
- Labeling language: Whether the FDA approves NASP broadly for uncontrolled gout or includes limitations; whether the label addresses ADA prevention as part of the mechanism
- Dose selection: Whether the FDA approves both doses or selects one (high dose showed higher response; low dose had similar efficacy in some subgroups)
- Sobi US launch: Pricing, distribution, patient support program, and specialty pharmacy network
- J-code assignment: Timing of permanent J-code from CMS will affect reimbursement
- Infusion center capacity: Whether rheumatology practices can accommodate a new every-4-week infusion therapy
- Krystexxa response: How Amgen positions Krystexxa against NASP (pricing, outcomes data, methotrexate co-treatment protocols)
- Platform potential: Whether the nanoencapsulated sirolimus ADA-prevention platform is applied to other biologics beyond pegadricase
- Real-world evidence: Post-marketing data on durability, ADA rates in clinical practice, and patient adherence to monthly infusions
Sources
- Sobi. "FDA Accepts Biologics License Application for Sobi's NASP for Patients with Uncontrolled Gout." September 10, 2025. https://www.sobi.com/en/press-releases/fda-accepts-biologics-license-application-sobis-nasp-patients-uncontrolled-gout-2389168
- ClinicalTrials.gov. "DISSOLVE I: NASP in Uncontrolled Gout." NCT04513366. https://clinicaltrials.gov/ct2/show/NCT04513366
- ClinicalTrials.gov. "DISSOLVE II: NASP in Uncontrolled Gout." NCT04596540. https://clinicaltrials.gov/ct2/show/NCT04596540
- Khanna P, et al. "Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Demonstrates a Reduction in Gout Flares: Results from the Phase 3 DISSOLVE Studies." Abstract 2588, ACR Convergence 2025. https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-nasp-demonstrates-a-reduction-in-gout-flares-results-from-the-phase-3-dissolve-studies
- Gaffo A, et al. "Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Reduces Disease Burden in Patients with Uncontrolled Gout." ACR Convergence 2025 Oral Presentation. https://sciencelibrary.sobi.com/sites/default/files/documents/Gaffo_2025_ACR_Oral_Presentation_FINAL.pdf
- Cleveland Clinic Journal of Medicine. "Nanoencapsulated Sirolimus Plus Pegadricase Reduced Disease Burden in Patients with Uncontrolled Gout." ACR 2025 coverage. https://www.ccjm.org/page/acr-2025/nanoencapsulated-sirolimus
- Rheumatology Advisor. "Novel Combo Therapy Under Review for Uncontrolled Gout." 2025. https://www.rheumatologyadvisor.com/news/novel-combo-therapy-under-review-for-uncontrolled-gout
- Rheumatology Advisor. "NASP Reduces Gout Flares in Patients with Uncontrolled Disease." 2025. https://www.rheumatologyadvisor.com/reports/nasp-reduces-gout-flares-in-uncontrolled-gout
- MedPath Trial. "FDA Accepts Sobi's NASP Biologics License Application for Uncontrolled Gout Treatment." 2025. https://trial.medpath.com/news/fda-accepts-sobi-s-nasp-biologics-license-application-for-uncontrolled-gout-treatment
- PMC. "Improvements in Patient-Reported Outcomes After Treatment with SEL-212 in Adults with Refractory Gout." https://pmc.ncbi.nlm.nih.gov/articles/PMC12963115
- MPR. "FDA Drug Approval Decisions Expected in June 2026." https://www.empr.com/news/fda-drug-approval-decisions-expected-in-june-2026
