Abstract: FR-PO1032
Effect of Lumasiran on Long-Term Clinical Outcomes in Primary Hyperoxaluria Type 1: A Cohort Simulation Model
Session Information
- Transplantation: Clinical - Pharmacology and Nonkidney Solid Organ Transplants
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Tencer, Tom, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
- De Francesco, Maria, HEOR Value Hub, Lanaken, Belgium
- Arteaga, Angela Maria, HEOR Value Hub, Lanaken, Belgium
- Doenges, Matthew, Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States
- Oh, Jun, UKE Hamburg, Hamburg, Germany
Background
In primary hyperoxaluria type 1 (PH1), a rare genetic disorder, hepatic oxalate overproduction can lead to chronic and end-stage kidney disease (CKD/ESKD). RNA interference therapeutic lumasiran, the first therapy approved for PH1 in all age groups, reduces urinary and plasma oxalate and maintains eGFR regardless of kidney function stage. We used modeling to simulate potential long-term effects of lumasiran therapy on clinical outcomes.
Methods
A Markov cohort simulation model was developed to assess lifetime ESKD, transplant, and mortality in lumasiran-treated (LT) vs not treated (NT) PH1 patients. It comprised 11 states by CKD stages, plasma oxalate levels, transplant status, and death; 6-month cycles were populated with data from phase 3 ILLUMINATE trials (NCT03681184, NCT03905694, NCT04152200), published literature, and local registries. Analyses were conducted for the overall population and stratified by CKD stage at lumasiran initiation. Adverse events were not included in the analysis.
Results
Average age at lumasiran initiation was 6.9 y in pediatric patients and 34 y in adults; 59% male, 63.7% in CKD stages 0-3b, 9.5% in CKD stage 4, and 26.8% with ESKD. Median time to death by cohort was 64.7 y in LT vs 30.8 y in NT. In patients with preserved kidney function at baseline, median time to ESKD events by cohort was 11.5 y in NT and not reached in LT. Furthermore, 10% in LT cohort and 92% in NT cohort progressed to ESKD, with lifetime transplant rates of 5% and 53%. In patients with advanced kidney disease at initiation, lifetime liver transplant rates by cohort were 16% in LT vs 66% in NT. Survival at 20 y was 76% in LT cohort vs 49% in NT cohort.
Conclusion
In the model, if reduction of oxalate is sustained beyond the 36 months that were observed in the ILLUMINATE trials, lumasiran may prolong survival and delay progression to ESKD in PH1 patients compared to natural history. Lumasiran may also reduce the need for liver and kidney transplants, particularly in patients with preserved renal function. The results suggest that early lumasiran initiation may offer long-term clinical benefits, potentially altering the disease course in PH1 and improving lifetime patient outcomes.
Funding
- Commercial Support – Alnylam Pharmaceuticals