Lumasiran (Oxlumo®), a first-in-class synthetic, double-stranded, ribonucleic acid (RNA) interference molecule targeting glycolate oxidase through silencing HAO1 mRNA, is approved in several countries for patients of any age and stage of kidney function with primary hyperoxaluria type 1 (PH1). Approval was based on results from the phase III ILLUMINATE trials. In the double-blind, placebo-controlled, ILLUMINATE-A trial, subcutaneous lumasiran was significantly more effective than placebo in reducing 24-h urinary oxalate excretion in patients aged ≥ 6 years with PH1; this effect was sustained for ≥ 36 months in ongoing longer-term analyses. In the single-arm ILLUMINATE-B trial, lumasiran reduced urinary oxalate:creatinine ratios and plasma oxalate levels in patients aged < 6 years with PH1. In the single-arm ILLUMINATE-C trial, lumasiran reduced plasma oxalate levels in patients with PH1 receiving dialysis as well as those not receiving dialysis. In secondary and exploratory analyses of these trials, nephrocalcinosis grade, kidney stone event rates and estimated glomerular filtration rates were either stable or improved with lumasiran. Lumasiran had an acceptable tolerability profile that remained consistent in longer-term analyses; the most common adverse events were mild and transient injection-site reactions. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1.
Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that leads to excess oxalate in urine or plasma requiring removal by the kidneys. This overproduction is damaging and can lead to kidney failure. Management of PH1 is typically not curative, eventually ending in kidney and/or liver transplantation. Lumasiran (Oxlumo®) is the first medicine to be approved in several countries for use in patients with PH1, regardless of their age or level of kidney function. It reduces liver oxalate production, lessening damage to the kidneys and potentially reducing the need for organ transplantation. In clinical trials, lumasiran was effective in reducing oxalate levels (in urine and/or plasma) in patients of all ages with PH1, and irrespective of whether they were receiving dialysis or not. Lumasiran either improved or stabilized the severity of calcium deposition in the kidneys, number of kidney stone events and kidney function. Lumasiran had an acceptable tolerability profile; the most common side effects were mild injection-site reactions that resolved quickly. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1.
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