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 m(2), age ≥ 6 years), 6 from DAILY-B (i.e., eGFR > 45 ml/min per 1.73 m(2), age < 6 years), and 10 from DAILY-C (i.e., all ages, eGFR < 45 ml/min per 1.73 m(2), 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.