Background/Purpose: Uricase-based therapies may profoundly lower serum uric acid (sUA) in patients (pts) with uncontrolled gout (UG) but often lead to anti-drug antibody (ADA) formation, which can predispose pts to infusion reactions (IRs). 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. NASP has shown efficacy and safety in UG (Baraf et al. Rheumatology 2024). To characterize events that met Rheumatology Common Toxicity Criteria for allergic reaction/hypersensitivity and anaphylaxis (Woodworth et al. J Rheumatol 2001), we show pt-specific IR details within 1 h of NASP completion from the phase 3 DISSOLVE I and II (NCT04513366, NCT04596540) studies.

Methods: DISSOLVE I and II were replicate, double-blind, placebo (PBO)-controlled trials evaluating 2 NAS doses (0.15 [high-dose; HD] or 0.1 mg/kg [low-dose; LD]) prior to 0.2 mg/kg P in adults with a UG diagnosis per ACR guidelines (Neogi et al. Arthritis Rheumatol 2015). Eligible pts had a history of symptomatic gout (≥3 gout flares within 18 mo of screening, ≥1 tophus, or current gouty arthritis), lack of sUA normalization and symptom control despite urate-lowering therapies, and sUA ≥7 mg/dL. Pts were randomized 1:1:1 to receive NASP (HD or LD) or PBO Q4W with preinfusion IR prophylaxis (up to six 4-wk treatment periods). Twenty-four–wk safety outcomes included IRs (eg, anaphylaxis, hypersensitivity) within 1 h per NIAID/FAAN criteria (Sampson et al. Ann Emerg Med 2006).

Results: Overall, 175 pts received HD (n=87) or LD (n=88) NASP; 90 received PBO. Of these, 7 pts (overall: n=7/175, 4.0%; HD NASP: n=3/87, 3.4%; LD NASP: n=4/88, 4.5%; PBO: n=0) had an IR within 1 h of NASP completion (all male; aged 36–63 y). Six IRs occurred shortly after exposure to both NASP components; 1 was during NAS only (pt did not receive P). All IRs were early in the study (first 12 wk). Of the 7 pts with IRs within 1 h, 4 had anaphylactic reactions (2.3% of NASP-treated pts overall; 2 in each NASP arm). Common signs/symptoms included rash and shortness of breath. Three of these IRs were grade (G) 3 (2 HD NASP; 1 LD NASP); 1 LD NASP-treated pt had a G4 IR. All pts fully recovered with appropriate medical intervention (mainly steroids and antihistamines) provided at the infusion center; 1 pt received epinephrine for anaphylaxis. One pt each in the HD/LD NASP arms (G3/G4 IRs, respectively) was sent to the emergency room, received observation only, and was discharged the same day. No pts required in-pt hospitalization or intubation. Three pts had hypersensitivity reactions (2 G1; 1 G2); signs/symptoms included flushing (most common) and shortness of breath (G2 only). No pts with hypersensitivity reactions were hospitalized; 1 pt was able to resume NASP after a pause.

Conclusion: 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).

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ACR Meeting Abstracts - 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/