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. 2024 Dec 30;10(4):1020-1036.
doi: 10.1016/j.ekir.2024.12.033. eCollection 2025 Apr.

Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort

Anne-Laure Sellier-Leclerc  1 , Melissa Cloarec  1 , Bertrand Knebelmann  2 , Lise Allard  3 , Olivia Boyer  4 , Sylvie Cloarec  5 , Claire Dossier  6 , Moglie Le Quintrec  7 , François Nobili  8 , Thomas Stehlé  9   10 , Isabelle Vrillon  11 , Stéphane Burtey  12   13 , Emilie Cornec-Le Gall  14   15 , Marie Courbebaisse  16   17 , Thierry Frouget  18 , Arnaud Garnier  19 , Thierry Krummel  20 , Sandrine Lemoine  1 , Catherine Monet-Didailler  21 , Caroline Rousset-Rouvière  22 , Amélie Ryckewaert  23 , Adeline Schendel  24 , Sacha Flammier  1 , Cécile Acquaviva-Bourdain  25 , Justine Bacchetta  1   26
Affiliations

Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort

Anne-Laure Sellier-Leclerc et al. Kidney Int Rep. .

Abstract

Introduction: Lumasiran is a drug used in RNA-interference (RNAi) therapy for primary hyperoxaluria type 1 (PH1). Data on its efficacy and safety mainly come from industry-sponsored trials.

Methods: For postmarketing follow-up, French authorities requested a quasi-exhaustive retrospective and prospective study over 5 years for patients receiving lumasiran, requiring the inclusion of at least 90% of patients, named as the DAILY-LUMA cohort (NCT06225882). Here, we analyzed data from all patients who were not previously included in the industry-sponsored trials and had received lumasiran for at least 2 years.

Results: We included 38 patients, 22 from DAILY-A (i.e., estimated glomerular filtration rate (eGFR) > 45 ml/min per 1.73 m2, age ≥ 6 years), 6 from DAILY-B (i.e., eGFR > 45 ml/min per 1.73 m2, age < 6 years), and 10 from DAILY-C (i.e., all ages, eGFR < 45 ml/min per 1.73 m2, 6 on dialysis). In DAILY-A and DAILY-B, decreased urinary oxalate-to-creatinine (UOx/creat) ratio, stable eGFR, and decrease in both nephrocalcinosis severity and stone numbers were observed, with a progressive tapering of conservative therapies. The decreased proportion of patients with nocturnal hydration and G-tubes overtime likely reflects improved quality of life. With a low number of patients - 2 patients on peritoneal dialysis and 3 patients with infantile oxalosis - the results are less conclusive for DAILY-C; however, in older patients, change in plasma oxalate (POx) levels is similar to previously published data. Tolerance was good with no severe side effects; injection site reactions, abdominal pain, and headaches were the main adverse events.

Conclusion: DAILY-LUMA is the largest cohort of patients receiving lumasiran in real life, confirming its safety and efficacy at 2 years.

Keywords: RNA interference; dialysis; hyperoxaluria type 1; lumasiran; real-life data; transplantation.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Flow-chart of the study. The numbers were updated on March 31, 2024. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.
Figure 2
Figure 2
DAILY-A Kids (Children aged 6–18 years, n = 13). (a and b) eGFR trends (global view and individual data). (c and d) UOx/creat trends (global view and individual data). (e) Trends in lithiasis numbers on ultrasound imaging. (f) Change in nephrocalcinosis on ultrasound imaging. M0-baseline versus M24 Wilcoxon matched-pairs signed rank test ∗∗P < 0.01; UOx/creatinine displayed as xx-times the upper limit for normal (ULN) for age. eGFR, estimated glomerular filtration rate; M, month; NC, nephrocalcinosis; UOx/creat, urinary oxalate-to-creatinine ratio.
Figure 3
Figure 3
DAILY-A adult patients (Adults aged > 18 years, n = 9). (a and b) eGFR trends (global view and individual data). (c and d) UOx/creat trends (global view and individual data). (e) Evolution of lithiasis numbers on ultrasound imaging. (f) Change in nephrocalcinosis on ultrasound imaging. M0-baseline vs. M24 Wilcoxon matched-pairs signed rank test ∗∗P < 0.01; UOx/creatinine displayed as xx-times the ULN for age. CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; eGFR, estimated glomerular filtration rate; M, month; NC, nephrocalcinosis; ULN, upper limit for normal; UOx/creat, urinary oxalate-to-creatinine ratio.
Figure 4
Figure 4
DAILY-B (Children aged < 6 years, n = 6). (a and b) eGFR trends (global view and individual data). (c and d) UOx/creat trends (global view and individual data). (e) Change in lithiasis numbers on ultrasound imaging. (f) Change in nephrocalcinosis on ultrasound imaging. Wilcoxon matched-pairs signed rank test M0-baseline vs. M24 ∗P < 0.05; UOx/creat displayed as xx-times the ULN for age. eGFR, estimated glomerular filtration rate; M, month; NC, nephrocalcinosis; ULN, upper limit for normal; UOx/creat, urinary oxalate-to-creatinine ratio.
Figure 5
Figure 5
DAILY-C – advanced CKD (n = 4). (a) eGFR trends in nondialysis patients. (b) UOx/creat trends. (c) POx trends in nondialysis patients. UOx trends in nondialysis patients. (d) Change in lithiasis numbers in nondialysis patients on ultrasound imaging. (e) Change in nephrocalcinosis in nondialysis patients on ultrasound imaging. The evaluation of patient in green may seem atypical: this patient was 3 months of age at lumasiran initiation, and the trends of POx levels paralleled the trends of eGFR. There was no lithiasis but bilateral nephrocalcinosis stage 1 from M0 to M6 of therapy; nephrocalcinosis disappeared at M9. UOx/creatinine displayed as xx-times the ULN for age. CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; M, month; NC, nephrocalcinosis; POx, plasma oxalate; ULN, upper limit for normal; UOx/creat, urinary oxalate-to-creatinine ratio.
Figure 6
Figure 6
DAILY-C dialysis patients. (a) POx trends in dialysis. (b) POx trends in (1) patients who begun lumasiran in dialysis and who were transplanted before 2 years of treatment (the last POx on the graph corresponds to the last POx available in the medical charts before transplantation) (n = 7), and (2) patients who begun lumasiran in dialysis currently before 2 years of treatment (the last POx on the graph corresponds to the last follow-up) (n = 7). (c) Change in lithiasis numbers on ultrasound imaging. (d) Change in nephrocalcinosis on ultrasound imaging. M, month; Pox, plasma oxalate.
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