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Abstract: PO1319

Modeling the Risk of Progression to Kidney Failure in Patients with Primary Hyperoxaluria Type 1 Treated with Lumasiran Relative to a Natural History Cohort Not Treated with Lumasiran

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Mara, Kristin C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Danese, David S., Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Gansner, John M., Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Lu, Jiandong, Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, United States
  • Milliner, Dawn S., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

In primary hyperoxaluria type 1 (PH1), the risk of kidney failure (KF) is positively associated with urinary oxalate (UOx) excretion. Lumasiran is an RNAi therapeutic to lower UOx levels in patients with PH1. We estimated the risk of progression to KF in patients with PH1 treated with lumasiran, relative to patients not treated with lumasiran.

Methods

A skewed-normal distribution of 24hr UOx values for patients with PH1 was simulated based on reported UOx values from the Rare Kidney Stone Consortium (RKSC) PH Registry among patients who were not in KF at diagnosis and did not receive lumasiran. Data from the ILLUMINATE-A trial of lumasiran were used to build a log-linear model of post-lumasiran treatment steady-state UOx as a function of baseline UOx. The distribution of steady-state, on-treatment UOx values for RKSC patients was then predicted by applying this model to the simulated 24hr UOx values of the RKSC cohort, considered as baseline. A risk model of KF as a function of 24hr UOx excretion, based on Kaplan-Meier curves of renal survival reported from the RKSC, was used to estimate the number of KF events/100 patients in the RKSC PH1 cohort, had all received lumasiran.

Results

The mean (SD) 24hr UOx excretion for the RKSC PH1 cohort was 2.2 (1.1) mmol/24hr/1.73m2 in the absence of lumasiran treatment and was predicted to decrease to 0.62 (0.17) mmol/24hr/1.73m2 in a model that simulated the effect of lumasiran administration (Figure 1). The predicted number of KF events/100 patients (95% CI) using the model for patients not treated with lumasiran at 10, 20 and 30 years, is 10 (4, 23), 32 (19, 50), and 42 (27, 59), respectively. In the model of lumasiran treatment, the estimated cumulative number of KF events/100 patients (95% CI) was 4 (1, 12) at 10 years and remained unchanged at 20 and 30 years.

Conclusion

This analysis predicts a long-term reduction in KF risk among PH1 patients treated with lumasiran, assuming prompt treatment at diagnosis.

Funding

  • Commercial Support