1814: Pegloticase for Uncontrolled Gout in Patients with History of Kidney Transplant: Pharmacokinetics and Immunogenicity in the PROTECT Clinical Trial

Abdul Abdellatif¹, Yan Xin², Jason Chamberlain³, Lin Zhao², Katya Cherny³, Brad Marder⁴, John D Scandling⁵ and kenneth saag⁶, ¹Kidney Hypertension Transplant Clinic Clear Lake Specialties, Webster, TX, ²Horizon Therapeutics, Deerfield, IL, ³Horizon Therapeutics plc, Deerfield, IL, ⁴Horizon Therapeutics, Denver, CO, ⁵Stanford University School of Medicine, Division of Nephrology, Palo Alto, CA, ⁶University of Alabama at Birmingham, Birmingham, AL

Background/Purpose: Immunomodulator co-therapy with pegloticase has been shown to reduce immunogenicity (anti-drug antibody [ADA] development), which markedly improves response rates with pegloticase while reducing risk for infusion reactions.^1-3 PROTECT (NCT04087720), an open-label, single-arm study in uncontrolled gout patients (pts) with functioning kidney transplant (KT) on stable immunosuppressants demonstrated that pegloticase was effective in reducing serum urate (SU) levels with a high (88.9% [95%CI: 65.3, 98.6]) responder rate while preserving key graft function indicators.⁴ The objective of this analysis was to evaluate the pharmacokinetics (PK) and immunogenicity of pegloticase in uncontrolled gout pts with a history of KT on immunosuppression.

Methods: Pegloticase (8 mg infusion [IV]) was administered every two weeks for 24 weeks. PK evaluation of pegloticase concentrations and immunogenicity of anti-monomethoxy-poly [ethylene glycol] (PEG) and anti-uricase IgG antibodies analysis was performed on serum samples. Responders were defined as pts achieving and maintaining a SU of < 6 mg/dL for at least 80% of time during Month 6. Two pts who withdrew consent due to coronavirus disease 2019 (COVID-19) concerns prior to Month 6 were not included in the responder analysis, per the statistical analysis plan.

Results: Twenty pts received at least 1 dose of pegloticase and were included in the analysis. The mean (SD) age was 53.9 (10.9) with the majority (90.0%) 40 to 81 years of age. Most were male (85.0%), 45.0% white, and 35.0% black or African American. Median baseline estimated glomerular filtration rate (eGFR) and baseline Urine Albumin-Creatinine Ratio (UACR) were 41.70 mL/min/1.73m² and 312.00 mg/g, respectively. Following treatment initiation, the median (min, max) pre-dose pegloticase concentration ranged from 0.97 (0.8, 1.9) µg/mL (at Week 2; n=20) to 1.59 (0.8, 4.1) µg/mL (at Week 14; n=15) and the median (min, max) post-dose pegloticase concentration ranged from 1.57 (1.0, 2.6) µg/mL (at Week 1; n=18) to 3.60 (2.0, 5.9) µg/mL (at Week 14; n=16) across visits. Measurable pegloticase concentrations were maintained in SU responders through Month 6. In contrast, the 2 non-responders both had pre-dose pegloticase concentrations below the limit of quantification (BLQ), and one had a BLQ value post-pegloticase infusion, which was consistent with the immunogenicity (ADA) results. No infusion reactions or anaphylaxis occurred during the trial.

Conclusion: Pegloticase exposures in kidney transplant patients on stable immunosuppression were higher than those previously observed on pegloticase monotherapy^1-3, which corresponded to the high clinical response rate previously reported for this kidney transplant patient cohort.⁴

References:
1. Keenan RT, et al. Seminars in Arthritis and Rheumatism 2021; 51:347-352
2. Botson J, et al. J Rheumatol 2021;48:767-74
3. Xin Y, et al. EULAR 2022; POS1163
4. Abdellatif A, et al. Amer Soc Neph; 2021, Abstract PO1127


Disclosures: A. Abdellatif, Amgen, Aurinia, Bayer, Horizon Therapeutics, Janssen, Keryx, Mallinckrodt, Merck, Natera, Opko, Rockwell, Vifor Pharma, Pharmacosmos; Y. Xin, Horizon Therapeutics; J. Chamberlain, Horizon Therapeutics; L. Zhao, Horizon Therapeutics; K. Cherny, Horizon Therapeutics; B. Marder, Horizon Therapeutics; J. Scandling, Horizon Therapeutics; k. saag, Horizon Therapeutics, SOBI, Shanton, AbbVie/Abbott.