On May 26th, Alnylam Pharmaceuticals announced that the FDA has accepted its marketing application for RNAi (RNAi) drug lumasiran for the treatment of type 1 primary hyperoxaluria (PH1), and granted priority review qualification, PDUFA scheduled approval period It was December 3, 2020.
Lumasiran is RNAi therapy targeting hydroxy acid oxidase 1 (HAO1), which can silence the expression of HAO1 gene, block the synthesis of glycolate oxidase (GO), and then inhibit the formation of oxalic acid in the liver by depleting GO. Since oxalic acid is a metabolite involved in the pathological process of PH1, lumasiran can prevent the progression of type 1 primary hyperoxaluria.
PH1 is a very rare disease. Excessive production of oxalate in patients leads to the deposition of calcium oxalate crystals in the kidneys and urinary tract, causing pain and repeated attacks of kidney stones and kidney calcification. The deposition of calcium oxalate and calcium oxalate stones can cause urinary tract obstruction, leading to renal tubular toxicity and kidney damage. Excessive oxalate cannot be effectively excreted in urine, which in turn will aggravate the condition, causing oxalate to accumulate and crystallize in bones, eyes, skin and heart, leading to more serious diseases and even death. The treatment of PH1 is very limited, including frequent renal dialysis, liver and kidney transplantation. Due to the availability of transplanted organs, the mortality rate after transplantation is also very high. In addition, a small number of patients can achieve complete remission after receiving vitamin B6 therapy. Currently, no therapy has been approved specifically for the treatment of PH1.
In December of last year, Alnylam announced that the phase III ILLUMINATE-A study of lumasiran for PH1 reached the primary efficacy endpoint and all secondary endpoints. The ILLUMINATE-A study enrolled 30 PH1 patients ≥6 years of age in 16 centers in 8 countries around the world. They were randomly assigned at a 2: 1 ratio and were given lumasiran 3 mg / kg (once every month for the first 3 months) , Once every 3 months thereafter) or placebo treatment. The primary end point was the difference from baseline in the 24-hour urinary oxalate excretion of the lumasiran treatment group during the 3rd to 6th month compared with the placebo group. The results showed that the study reached the primary endpoint (p <0.0001).
In addition, the proportion of patients with oxalic acid levels near normalization or normalization in the lumasiran treatment group was significantly higher than that in the placebo group. In the study, no serious adverse events occurred, and lumasiran showed encouraging safety and tolerability, and the overall situation was consistent with that observed in phase I / II and open label extension studies.
Lumasiran is developed using Alnylam's latest Enhanced Stability Chemistry (ESC) -GalNAc conjugation technology. It has a stronger and longer lasting effect when administered subcutaneously and has a wider therapeutic index. Lumasiran has been granted orphan drug qualifications for the treatment of PH1 in the United States and the European Union. It has also received the breakthrough drug qualification granted by the FDA and the priority drug qualification (PRIME) granted by EMA.
