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Lumasiran data by EOYAlnylam sees the light Alnylam is due to report from its pivotal Illuminate-A trial of lumasiran in primary hyperoxaluria type 1 (PH1), a rare inherited disease, by the end of the year. Lumasiran is an RNAi therapeutic designed to reduce levels of the enzyme glycolate oxidase, preventing the formation of oxalate; in PH1 this substance builds up in combination with calcium to form kidney and bladder stones, causing kidney problems and, eventually, end-stage renal disease. There are three types of primary hyperoxaluria that differ in severity and genetic cause. Lumasiran targets only PH1, which is caused by a mutation in the AGXT gene. There are no approved therapies for the disease, and some patients have to undergo liver and kidney transplants. The Illuminate trial compares subcutaneous lumasiran versus placebo in 30 adults and children. The primary measure is the percentage change in 24-hour urinary oxalate excretion from baseline to 6 months, a surrogate endpoint. Key secondary endpoints include additional measures of urinary oxalate, estimated glomerular filtration rate, safety and tolerability. In terms of competition lumasiran is neck and neck with Dicerna’s DCR-PHXC, another RNAi contender that is in a pivotal trial called Phyox2 in 36 patients with PH1 and PH2. Dicerna hopes that its candidate could be used in all genetic subtypes of PH. DCR-PHXC targets a different enzyme, lactate dehydrogenase A, inhibition of which is said to reduce oxalate levels. Dicerna’s trial also uses the 24-hour urinary oxalate excretion as an endpoint, but the study measures levels at 3, 4, 5 and 6 months to give an average value over time; this could help mitigate variability and placebo effect. If Illuminate-A proves positive Alnylam expects to file early next year.
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