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Lumasiran for Advanced Primary Hyperoxaluria Type 1

A first-in-class small interfering RNA (siRNA), lumasiran was safe and effective in a phase 3 trial for reducing urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C used an open-label, single-arm design and included patients of all ages with PH1 and advanced kidney disease, including those with or without systemic oxalosis.

Given as 3 monthly subcutaneous doses followed by monthly or quarterly weight-based dosing, lumasiran produced these changes in a primary end point of percentage change in POx from baseline to month 6 in cohorts not on dialysis at baseline (cohort A) and receiving dialysis at enrollment (cohort B): “All patients (N = 21; 43% female; 76% White) completed the 6-month primary analysis period. Median age at consent was 8 (range, 0-59) years. For the primary end point, least-squares mean reductions in POx were 33.3% (95% CI, −15.2% to 81.8%) in cohort A (n = 6) and 42.4% (95% CI, 34.2%-50.7%) in cohort B (n = 15). Improvements were also observed in all pharmacodynamic secondary end points. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all of which were mild and transient.”

Editorial: “As PH1 patients across the spectrum of chronic kidney disease are treated with siRNA, it will also be paramount to study its use and learn from its provision outside of the setting of a controlled clinical trial,” writes an editorialist. “Optimization of clinical management in a rare disease such as PH1 requires broad collaboration among clinicians, ready sharing of pertinent data, and a focus on key patient outcomes. Accordingly, the development of new therapies underscores the need for existing PH1 patient registries to develop close working relationships to study the clinical impact of changes in PH1 management so that therapeutic advances come to be applied in the most efficacious, beneficial, and equitable fashion.”

Source: American Journal of Kidney Diseases