pegsiticase/SVP-rapamycin (SEL212) / SOBI, Cartesian Therapeutics - LARVOL DELTA

Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Reduces Gout Clinical Manifestations in Patients with Uncontrolled Gout (UG) and Stage 3 CKD (KIDNEY WEEK 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of targeted nanoencapsulated sirolimus (NAS) and pegadricase (P) that reduces serum uric acid (sUA). Safety was similar to the ITT population ( Table ), with only one case of proteinuria in each NASP arm (not considered drug related). Conclusion NASP was well tolerated and reduced disease burden in pts with UG and CKD."

Clinical • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology

Nanoencapsulated Sirolimus Plus Pegadricase Reduced Disease Burden in Patients With Uncontrolled Gout: Results From the Phase 3 DISSOLVE Trials (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of targeted nanoencapsulated sirolimus (NAS, formerly SEL-110), which mitigates the formation of antipegadricase antibodies, and a uricase (pegadricase [P]; formerly SEL-037), which reduces sUA. NASP-treated pts had meaningful reductions in disease burden and key clinical manifestations, as reflected by improvements in sUA levels and PROs. This therapy has a noteworthy impact on resolving acute gout symptoms over 6 treatments and shows promise for improving HRQOL."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Reduction in Tophi Observed in Patients with Uncontrolled Gout Treated with NASP: Results from Phase 3 DISSOLVE Studies (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is a novel, every 4-week, sequential infusion therapy consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS; formerly SEL-110) co-administered with a pegylated uricase (formerly SEL-037) designed to reduce serum uric acid (sUA) levels in pts with UG. Treatment with NASP resulted in a greater tophus response compared to PBO. In addition, a robust sUA reduction, a key factor in tophus resolution, was observed in NASP-treated pts. These results highlight the effectiveness of NASP in lowering sUA and promoting tophus resolution."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Rheumatology

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 (ACR Convergence 2025) - P3 | "Nanoencapsulated sirolimus plus pegadricase (NASP, formerly SEL-212) is a novel investigational therapy delivered every 4 weeks as a sequential, two-component infusion consisting of targeted nanoencapsulated sirolimus and pegadricase, a pegylated uricase (Figure 1A). These data support the long-term durability of NASP as shown by sustained sUA reductions and decreased gout flares over time, with 100% on HD NASP and 92.3% on LD NASP being flare-free at the end of the extension phase. NASP was generally well tolerated with low discontinuation rates during the extension phase. Overall, NASP led to improvements in key clinical manifestations of UG."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Nanoencapsulated Sirolimus plus Pegadricase (NASP) Demonstrates a Reduction in Gout Flares: Results from the Phase 3 DISSOLVE Studies (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, every 4-week, sequential infusion therapy designed to reduce sUA levels in patients (pts) with uncontrolled gout (UG), consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS; formerly SEL-110), sequentially administered with pegadricase (a pegylated uricase; formerly SEL-037). The proportion of pts with flares and number of flares decreased with NASP compared to PBO over the course of the study, with 95.2% and 94.3% of HD and LD-treated pts being flare-free during weeks 21–24. These results highlight the potential of NASP as an effective therapy for reducing disease burden and improving a key clinical outcome in pts with UG."

P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

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 (ACR Convergence 2025) - P3 | "NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of tolerogenic nanoencapsulated sirolimus (NAS, formerly SEL-110), which mitigates formation of antipegadricase antibodies, and a uricase (pegadricase [P]; formerly SEL-037), which reduces sUA...All pts fully recovered with appropriate medical intervention (mainly steroids and antihistamines) provided at the infusion center; 1 pt received epinephrine for anaphylaxis... The low incidence (4.0%) of pts experiencing IRs, including hypersensitivity reactions, within 1 h of NASP suggests that NAS mitigates ADA formation. No pts required in-patient hospitalization or intubation, and all IRs resolved with standard measures (mainly at the infusion center)."

P3 data • Gout • Immunology • Inflammatory Arthritis • Rheumatology

FDA Accepts Biologics License Application for Sobi's NASP for Patients with Uncontrolled Gout (Sobi Press Release) - "The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action date of 27 June 2026....The submission included results from the Phase 3 DISSOLVE I & II placebo controlled randomized clinical trials evaluating safety and efficacy of two different dose levels of NASP in adult patients with uncontrolled gout."

FDA filing • PDUFA • Gout

Impact of Anti-drug Antibodies on the Efficacy of SEL-212 in Patients with Chronic Gout Refractory to Conventional Therapy (ACR Convergence 2024) - P3 | "Background/Purpose: SEL-212 is a once-monthly, investigational, two-component infusion therapy consisting of pegadricase (SEL-037, a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus (SEL-110), for the treatment of patients with chronic gout refractory to conventional therapy. In the DISSOLVE studies, SEL-110 mitigated ADA formation for up to 12 months of treatment, allowing for sUA control in patients with chronic gout refractory to conventional therapy treated with SEL-212. Anti-uricase ADAs were the most common, as expected. However, loss of sUA control was typically restricted to high-titer anti-uricase ADAs and IRs were few, making this combination therapy a promising option for patients with severe gout."

Clinical • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Safety and Efficacy of SEL-212 in the US and ex-US Subgroups: Results from the Phase 3 DISSOLVE Studies (ACR Convergence 2024) - P3 | "Background/Purpose: The DISSOLVE Phase 3 study program investigated the efficacy and safety of SEL-212, a novel, once-monthly, two-component infusion therapy consisting of pegadricase (SEL-037, a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus (SEL-110), in United States (US) and Eastern European patients with chronic gout refractory to conventional therapy. This post hoc analysis of the DISSOLVE studies suggests that SEL-212 is safe and effective at lowering sUA in patients in both regions, including in those patients with a higher disease burden at baseline, as demonstrated by the number of swollen and tender joints, HAQ-DI and SF-36 PCS scores. The findings support SEL-212 as a potential novel once-monthly treatment option that can alleviate the disease burden of chronic gout refractory to conventional therapy."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Improvements in Patient-Reported Outcomes After Treatment with SEL-212 in Adults with Refractory Gout: Results from Two Randomized Phase 3 Trials (ACR Convergence 2024) - "SEL-212 is a novel, once-monthly, two-component infusion therapy of nanoparticles containing sirolimus (SEL-110) followed by pegadricase (SEL‑037, a pegylated uricase) designed to reduce sUA. Clinically meaningful changes in PROs were reported after 3 doses of SEL-212, which further improved after 3 additional doses, indicating patients reported an incremental HRQoL benefit with prolonged treatment duration. SEL-212 improved clinical and HRQoL outcomes, including functional ability, mental health and pain, in adults with refractory gout, which is likely reflective of improved urate lowering with this novel agent."

Clinical • P3 data • Patient reported outcomes • Gout • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatology

Efficacy and Safety of SEL-212 in Patients with Refractory Gout and CKD: A Post Hoc Analysis from the Two Phase 3 DISSOLVE Studies (KIDNEY WEEK 2024) - P3 | "Here, we present Phase 3 efficacy and safety data on the investigational uricase-based therapy SEL-212 in patients with CRG and CKD. DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540) investigated the efficacy and safety of SEL-212, a two-component infusion therapy of pegadricase (a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus in the treatment of CRG. Data from DISSOLVE I and II endorsed the efficacy and safety of SEL-212 in patients with gout refractory to conventional therapy with CKD stage 3. Further studies are needed to establish the use of this novel combination product in refractory gout with end-stage kidney damage."

Clinical • P3 data • Retrospective data • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Rheumatology

ONCE-MONTHLY SEL-212 DEMONSTRATES EFFICACY AND SAFETY FOR UP TO 6-MONTHS IN GOUT REFRACTORY TO CONVENTIONAL THERAPY: COMBINED DATA FROM THE DISSOLVE I & II PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIALS (EULAR 2024) - "SEL-212 is a novel, once-monthly therapeutic platform that consists of sequential infusions of immune-tolerising nanoparticles containing sirolimus (SEL-110), followed by a pegylated uricase (pegadricase, SEL-037). Combined DISSOLVE I & II data confirm the results from the individual studies. Both SEL-212 doses demonstrated clinical efficacy and safety. The lower proportion of patients meeting the stopping rule with HD vs LD SEL-212 suggests that HD SEL-212 may be more efficacious."

Clinical • P3 data • Dental Disorders • Gout • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Pain • Rheumatology • Stomatitis

LONG-TERM IMPROVEMENTS IN SERUM URIC ACID LEVELS, GOUT SYMPTOMS, AND SAFETY UP TO 12-MONTHS WITH SEL-212 IN GOUT REFRACTORY TO CONVENTIONAL THERAPY: RESULTS FROM THE DISSOLVE I PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL (EULAR 2024) - "SEL-212 is a novel, once-monthly treatment of sequential infusions of immune-tolerising, sirolimus-containing nanoparticles (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). SEL-212 efficacy was maintained over the 12-month follow-up period and no new safety signals were observed, suggesting that investigational SEL-212 has the potential to be an effective therapy for patients with refractory gout. Once-monthly dosing, and the novel use of sirolimus-containing nanoparticles to mitigate against the development of anti-uricase immunity, differentiates SEL-212 from the currently-approved uricase therapy."

Clinical • P3 data • Dental Disorders • Gout • Inflammatory Arthritis • Rheumatology • Stomatitis

HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND OTHER SECONDARY CLINICAL OUTCOMES IN ADULTS WITH GOUT REFRACTORY TO CONVENTIONAL THERAPY TREATED WITH SEL-212: POOLED 6-MONTH DATA FROM THE PHASE 3 DISSOLVE I & II CLINICAL TRIALS (EULAR 2024) - "SEL-212 is a novel, once-monthly uricase-based therapy comprising sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase; SEL-037). Aggregated data from DISSOLVE I & II demonstrate improvements in HRQoL and tender joint count in patients with gout refractory to standard therapy treated with both doses of SEL-212. Similar gout flare incidence during the first three months and subsequent reductions in flare frequency by the end of the study indicate a decline in the body's burden of urate over time."

Clinical • Clinical data • HEOR • P3 data • Gout • Inflammatory Arthritis • Pain • Rheumatology

Gout symptom improvements and patient outcomes with SEL-212 in gout refractory to conventional therapy: DISSOLVE I & II phase 3, double-blind, placebo-controlled clinical trials (BSR 2024) - "SEL-212 is a novel, once-monthly treatment of sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). SEL-212 was well tolerated and provided significant reductions in mean sUA over time, improvement in SF-36 physical and HAQ-DI measures and reduced the number of tender/swollen joints."

Clinical • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Safety & Efficacy of SEL-212 in Patients with Gout Refractory to Conventional Treatment: Primary Outcomes from Two Randomized, Double Blind, Placebo-Controlled, Multicenter Phase 3 Studies (ACR Convergence 2023) - "SEL-212 consists of an infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) followed by pegadricase (SEL-037). In the DISSOLVE trials, once-monthly treatment with SEL-212 demonstrated statistically significant response rates and reductions in sUA versus placebo. The safety profile of SEL-212 was consistent with that of uricase therapies. Targeted immunomodulation with SEL-212 has the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies."

Clinical • P3 data • Gout • Immunology • Inflammatory Arthritis • Novel Coronavirus Disease • Rheumatology

The COMPARE head-to-head, randomised-controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout. (PubMed, Rheumatology (Oxford)) - P2 | "SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with substantial reduction in treatment burden with SEL-212, due to decreased infusion frequency vs pegloticase."

Head-to-Head • Journal • Dental Disorders • Gout • Infectious Disease • Inflammatory Arthritis • Rheumatology • Stomatitis

SAFETY & EFFICACY OF SEL-212 IN PATIENTS WITH GOUT REFRACTORY TO COVENTIONAL TREATMENT: OUTCOMES FROM TWO RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED, MULTICENTER PHASE III STUDIES (EULAR 2023) - "SEL-212 consists of an infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) followed by pegadricase (SEL-037). In the DISSOLVE trials, once-monthly treatment with SEL-212 demonstrated statistically significant response rates and reductions in sUA versus placebo. The safety profile of SEL-212 was consistent with that of uricase therapies. Targeted immunomodulation with SEL-212 has the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies without the need for traditional immunosuppressants."

Clinical • Late-breaking abstract • P3 data • Gout • Immune Modulation • Inflammatory Arthritis • Rheumatology

DISSOLVE II: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II (clinicaltrials.gov) - P3 | N=153 | Completed | Sponsor: Selecta Biosciences, Inc. | Recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Jan 2023 | Trial primary completion date: Sep 2022 ➔ Jan 2023

Trial completion • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3 | N=112 | Completed | Sponsor: Selecta Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Gout • Inflammatory Arthritis • Rheumatology

Phase 2 Dose-Finding Study in Patients with Gout Using SEL-212, a Novel PEGylated Uricase (SEL-037) Combined with Tolerogenic Nanoparticles (SEL-110). (PubMed, Rheumatol Ther) - P2 | "Results provide continued support for the use of multiple monthly administrations of SEL-037 0.2 mg/kg + SEL-110 0.1-0.15 mg/kg in clinical trials for SEL-212."

Journal • P2 data • Gout • Inflammatory Arthritis • Rheumatology

"$SELB Phase 3 DISSOLVE Program of SEL-212 in Chronic Refractory Gout Meets Primary Endpoint https://t.co/u8c7PmbUim" (@stock_titan)

Gout • Inflammatory Arthritis • Rheumatology

"$SELB topline data for Phase 3 DISSOLVE I & II trials of SEL-212 in chronic refractory gout on track for Q1" (@BioStocks)

P3 data • P3 data: top line • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE I: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (clinicaltrials.gov) - P3 | N=120 | Active, not recruiting | Sponsor: Selecta Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gout • Inflammatory Arthritis • Rheumatology

DISSOLVE II: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Selecta Biosciences, Inc. | Trial completion date: May 2022 ➔ Sep 2022 | Trial primary completion date: May 2022 ➔ Sep 2022

Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology