Alnylam's third RNAi therapy lumasiran is about to be approved by the European Union

Alnylam Pharmaceuticals is a global leader in the development of RNAi therapies, and its drug Onpattro (patisiran, intravenous preparation) was approved in August 2018, making it the first RNAi drug to be approved for sale in a full 20 years since the RNAi phenomenon was discovered. In November 2019, its drug Givosirari (givosiran, subsescape preparation) was approved, becoming the second RNAi drug approved worldwide and the first global approval of GalNAc-linked RNA therapy, marking a major milestone in the development of precision gene drugs.Alnylam recently announced that the European Medicines Agency (EMA) Human Pharmaceutical Products Committee (CHMP) has issued a positive review recommending the approval of the RNAi drug lumasiran for the treatment of primary high herbic acid uremia Type 1 (PH1). The European Commission is expected to make a final review decision in the fourth quarter of 2020. If approved, lumasiran will be sold in Europe under the product name Oxlumo.Currently, lumasiran is also under priority review by the FDA, with a target date of December 3, 2020 for the Prescription Drug User Charge Act (PDUFA). In the United States, lumasiran has been awarded the FDA's pediatric rare disease eligibility for PH1 treatment, orphan drug eligibility (ODD), breakthrough drug qualification (BTD). In the European Union, lumasiran has been granted ODD, Priority Drug Qualification (PRIME).Primary high herb uric acid type 1 (PH1) is a portable and devastating disease, and liver transplantation is the only treatment to solve the root cause of the disease. The disease is a very rare, life-threatening disease that affects the kidneys and other vital organs, affecting infants, children and adults, and patients face repeated and painful stone events, as well as repeated and unpredictable declines in kidney function, which eventually lead to end-stage kidney disease that requires intensive dialysis as a bridge for double liver/kidney transplantation.lumasiran is the first potential therapy to show a significant reduction in urinary acid excretion. Results from the Phase III ILLUMINATE-A study (NCT03681184) show that lumasiran significantly reduces the production of hertic acid in the liver and may solve the inherent pathophysiological problems of PH1. If approved, lumasiran will have a meaningful clinical impact on PH1 patients.CHMP's positive comments are based on the results of ILLUMINATE-A. This is a randomized, double-blind, placebo-controlled trial involving 30 PH1 patients aged ≥6 at 16 clinical centers in eight countries around the world, the largest interventional study in the PH1 group. In the study, patients were randomly assigned a 2:1 ratio to be treated with lumasiran or a placebo. lumasiran is given at a dose of 3 mg/kg, treated once a month for 3 months, and then maintained at a quarterly dose. The main endpoint was a percentage change in the 24-hour uric acid excretion compared to the baseline during the 3rd to 6th months of the lumasiran treatment group compared to the placebo group.The results showed that the study reached the main < (p)0.0001). In addition, the study achieved statistically significant results (p< or 0.001) on the secondary endpoints of all six stratified tests, including the proportion of patients in the lumasiran treatment group who achieved near or normalized uric acid levels compared to the placebo group. In the study, no serious adverse events occurred, and lumasiran showed encouraging safety and tolerance, consistent with what was observed in the Phase I/II and Open Label Extension studies. The full results of the study are scheduled to be presented at the OxalEurope International Conference, currently scheduled for 16 June 2020 in Amsterdam.PH1 is a super-rare disease that causes kidney failure due to excessive ratic acid production and has significant morbidity and mortality, and there is currently no approved treatment. PH1 usually occurs in childhood and requires immediate and effective intervention, with late-stage patients have no choice but dialysis.lumasiran is a subsurface injection RNAi drug targeting hydroxy acid oxidase 1 (HAO1) and developed for the treatment of primary high oxalic aciduria type 1 (PH1). HAO1 encodes ethanolate oxidase (GO). Thus, by silencing HAO1 and consuming GO enzymes, lumasiran inhibits and normalizes the production of oxalic acid (a metabolite directly involved in PH1 pathophysiology) in the liver, potentially preventing the progression of PH1 disease.Lumasiran has been developed using Alnylam's latest enhanced stable chemical ESC-GalNAc conjugate technology, which makes endembering drug dissosis more effective and durable, with a broad therapeutic index. Alnylam is currently conducting two other global Phase III studies: (1) ILLUMINATE-B, which evaluates PH1 patients aged <6 years of age treated by lumasiran, the main results of which were announced in September. (2) ILLUMINATE-C, which evaluates patients with PH1 of all ages with advanced kidney disease treated with lumosiran treatment, is expected to receive results in 2021. (Bio Valley Bioon .com)original source: Alnylam Receives Positive CHMP Opinion for OXLUMO? (lumasiran) for the Treatment of Primary Hyperoxaluria Type 1 in All Age Groups