Application for FDA priority review for RNAi treatment with high oxalic acid uric acid

Lumasiran is a targeted hydroxy acid oxidase 1 (HAO1) RNAi therapy, can silence the EXPRESSION of the HAO1 gene, block the coding synthesis of ethanol acid oxidase (GO), and then by depleting GO to inhibit the formation of oxalic acid in the liverSince oxalic acid is a metabolite involved in the PH1 pathological process, lumasiran can prevent the progression of type 1 primary high uremiaPH1 is an extremely rare disease in which excessive oxalate production in patients causes calcium oxalate crystals to be deposited in the kidneys and urinary tracts, causing pain and recurrent seizures of kidney stones and renal calciumThe deposition of calcium oxalate and calcium oxalate stones can cause urinary tract blockage, leading to the toxicity of the kidney tube, resulting in kidney damageExcess oxalate sits cannot be excreted effectively through urine, which in turn exacerbates the condition, causing oxalate to accumulate and crystallize in bones, eyes, skin and heart, leading to more serious diseases and even deathTreatment of PH1 is very limited, including frequent kidney dialysis, liver and kidney transplantsDue to the availability of transplanted organs, the mortality rate after transplantation is also very highIn addition, a small number of patients receivevitamin B6 therapy can achieve complete remissionAt present, no treatment has been approved specifically for the treatment of PH1December, Alnylam announced that the Phase III ILLUMINATE-A study of lumasiran's treatment of PH1 had reached the primary therapeutic end and all secondary endpointsThe ILLUMINATE-A study enrolled 30 PH1 patients aged 6 years in 16 centers in eight countries worldwide, assigned 3 mg/kg (1 month in the first 3 months and 1 time every 3 months after the first 3 months) or placebo treatment at a 2:1 ratioThe main endpoint was the difference between the lumasiran treatment group and the placebo group for 24 hours of urinary acid excretion over the baseline period from 3 to 6 monthsThe results showed that the study reached the main endpoint (p 0.0001)in addition,, the proportion of patients in the lumasiran treatment group whose levels of oxalic acid was close to normalization or normalized was significantly higher than in the placebo groupIn the study, no serious adverse events occurred, lumasiran showed encouraging safety and tolerance, and the overall picture was consistent with the observations observed in the Phase I/II and Open Label Extension studieslumasiran uses Alnylam's latest enhanced stabilization chemistry (ESC)-GalNAc conjugate technology, which has stronger and longer-lasting results when injected under the skin and has a wider therapeutic index Lumasiran has been awarded orphan drug for PH1 in both the United States and the European Union, as well as the FDA-awarded Breakthrough Drug And THE EMA-granted Priority Drug (PRIME).