1. Lumasiran was shown to decrease urinary oxalate excretion in patients with Primary Hyperoxaluria Type 1.
2. Lumasiran was shown not to cause severe or serious adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Oxalate is the toxic metabolite overproduced by the liver in Primary Hyperoxaluria Type 1 (PH1). The elevated levels lead to kidney stones, nephrocalcinosis, and end-stage kidney disease. This trial studied the safety and efficacy of lumasiran, an RNA interference therapeutic agent, for the management of PH1 patients. The trial determined a significant decrease in 24-hour urinary oxalate excretion from baseline to end of the study. As for safety, most patients reported injection-site reactions, but no severe or serious adverse events were reported. A major limitation of this study is the exclusion of patients with stage four kidney disease. Nonetheless, the trial provided evidence for the use of lumasiran in patients with PH1 for preserving kidney function. As oxalate is the key toxic metabolite in PH1, targeting this specifically will result in long-term clinical benefits for patients.
Relevant Reading: Lumarisan: First Approval
In-Depth [randomized controlled trial]: This multinational, randomized controlled trial enrolled 39 patients from 16 sites in eight countries. Patients with a confirmed PH1 diagnosis by genetic testing, over six years of age, and a 24-hour urinary oxalate of at least 0.07millimole were eligible for participation in the trial. Patients with clinical evidence of extrarenal systemic oxalosis were excluded from the study. Patients were randomized in a 2:1 ratio to receive lumasiran or placebo, respectively. The primary endpoint was the percent change in 24-hour urinary oxalate excretion from baseline to end of the trial at six months. The least-squares mean percent change -65.4% in the lumasiran group and -11.8% in the placebo group (least-squares mean difference, -53.5 percentage points; 95% confidence interval [CI], -62.3 to -44.8; P < 0.001). In addition, 84% of patients treated with lumasiran had a urinary oxalate level lower than 1.5 times the upper limit of normal at six months compared to 0% of patients in the placebo group (P < 0.001). The plasma oxalate levels was significantly lower in the treatment group compared to the placebo group (least-squares mean difference, -39.5 percentage points; 95% CI, -50.1 to -28.9; P < 0.001). Lastly, lumasiran treatment was shown to be safe as no severe or serious adverse events or deaths occurred during the trial. The most common side effect reported was injection-site reactions which occurred in 10 patients (38%) from the lumasiran group and 0 (0%) from the placebo group. Overall, lumasiran treatment was shown to decrease urinary oxalate excretion in patients with Primary Hyperoxaluria Type 1 without end-stage kidney disease.
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