506 - Descriptive Analysis of Real-World Enrollment Data of Pediatric and Adult Patients From a Global Primary Hyperoxaluria Type 1 Registry (BONAPH1DE)

Publication Number: 2492.506

Efrat Ben-Shalom, Shaare Zedek Medical Center, Jerusalem, Yerushalayim, Israel; John C. Lieske, Mayo Clinic Alix School of Medicine, Rochester, MN, United States; Michelle A. Baum, Boston Children's Hospital, Boston, MA, United States; Vladimir Belostotsky, McMaster Children's Hospital, Hamilton, ON, Canada; Felix Knauf, Mayo Clinic Alix School of Medicine, Rochester, MN, United States; Anne-Laure Sellier-Leclerc, AdventHealth for Children, BRON, Rhone-Alpes, France; Weiming Du, Alnylam Pharmaceuticals, Basking Ridge, NJ, United States; Mary Callanan, Alnylam, Cambridge, MA, United States; Teresa Kauf, Alnylam Pharmaceuticals, inc, Cambridge, MA, United States; Raymond Doan, Alnylam Pharmaceuticals, Inc., San Francisco, CA, United States; Jeffrey Saland, The Mount Sinai Kravis Children's Hospital, New York, NY, United States; Jaap W. Groothoff, Amsterdam UMC, AMSTERDAM, Noord-Holland, Netherlands

Background: Primary hyperoxaluria type 1 (PH1) causes hepatic oxalate overproduction, often leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. BONAPH1DE (NCT04982393) is a PH1 registry in a broad population, including patients (pts) with limited or no clinical trial data.

Objective: Here, we characterize enrollment data from the BONAPH1DE registry.

Design/Methods: Eligible pts have confirmed PH1 managed per routine clinical practice and are enrolled in Belgium, Canada, France, Germany, Italy, Israel, Netherlands, Spain, Switzerland, UK, and US. Data are retrospectively collected up to 5 years pre-enrollment, at enrollment, and prospectively annually up to 7 years. Measures include demographics; genetic testing; manifestations; comorbidities; management; laboratory results (eg, eGFR [calculated using serum creatinine]); pt-reported outcomes; healthcare resource utilization; and safety, pregnancy, and birth outcomes. Pts with no lumasiran treatment history or who underwent liver transplant before enrollment were excluded from this analysis.

Results: From December 13, 2021 to November 18, 2024, 82 pediatric and 42 adult pts of 138 enrolled had lumasiran treatment history. Family history of PH1 was reported for 39 (48%) pediatric and 16 (38%) adult pts. Twenty-one (26%) pediatric and 22 (52%) adult pts had a pyridoxine-responsive–associated genotype (PR/PR or PR/-). Mean (SD) diagnosis ages (pediatric/adult) were 3.3 (3.9)/22.1 (19.1) years, symptom onset to diagnosis times were 0.7 (1.7)/8.1 (12.5) years, and diagnosis to lumasiran treatment times were 3.0 (3.5)/11.5 (11.4) years. PH1 treatments at enrollment included lumasiran (pediatric/adult: 95%/95%), pyridoxine (42%/67%), crystallization inhibitors (51%/24%), hyperhydration (37%/33%), and dialysis (16%/19%). Before lumasiran treatment, mean (SD) eGFR (n=66/n=20) was 67.61 (43.66)/57.82 (30.32) mL/min/1.73m2 and spot urinary oxalate:creatinine (n=29/n=6) was 0.46 (0.47)/0.09 (0.08) mmol/mmol. Baseline kidney function was normal to stage 5 chronic kidney disease. Many pts had a history of kidney stones (pediatric/adult: 34 [42%]/30 [71%]), nephrocalcinosis (35 [43%]/12 [29%]), or kidney transplant (5 [6%]/5 [12%]).

Conclusion(s): Data suggest differences in time from diagnosis to lumasiran treatment in pediatric and adult pts. BONAPH1DE complements existing registries by analyzing global pt characteristics and capturing long-term PH1-treatment data in routine clinical management. Future analyses will evaluate real-world effectiveness in adult and pediatric PH1 pts.