The world's first RNAi drug! Alpantro, an Alnylam drug, has been applied for marketing in Brazil for the treatment of HTTR amyloidosis

October 11, 2019 / BIOON / - Alnylam Pharmaceutical Co., Ltd is a leading enterprise in the field of RNAi therapy development Recently, the company announced that it has submitted the marketing approval application (MAA) of onpattro (paisiran) to Anvisa for the treatment of amyloidosis with polyneuropathy mediated by hereditary thyroxine transfer protein (HTTR) Onpattro has been given priority review by Anvisa Alnylam expects Anvisa to make a review decision in the first half of 2020 Onpattro is the first investigational drug submitted by Alnylam for review in Brazil If approved, it will be the first product sold by Alnylam in the country, and also the first RNAi drug approved in Latin America Norton Oliveira, Latin American director and senior vice president of Alnylam, said: "our application for registration of onpattro in Brazil is an important step for us to continue to work on bringing RNAi treatment technology to people all over the world Atatr amyloidosis is a rare progressive disease that is considered endemic in Brazil and affects more than 5000 people The symptoms of the disease can be expressed in the whole body and have a devastating impact on the patient We look forward to working closely with Anvisa to bring onpattro to these patients in need as soon as possible " This Brazilian registration application is based on the data of Apollo, a phase III clinical study The study was a randomized, double-blind, placebo-controlled, global study conducted in patients with atatr amyloidosis with polyneuropathy to assess the efficacy and safety of patisiran A total of 225 patients with atatr amyloidosis with polyneuropathy were enrolled in this study, covering 39 genotypes In the study, patients were randomly assigned to patisiran (0.3mg/kg, once every three weeks) and placebo treatment in a 2:1 ratio The primary end point of the study was the change in the modified neuropathy impairment score (mnis + 7) relative to baseline at the 18th month of treatment Mnis + 7 is a comprehensive measure of neurological deficit, which evaluates sensory motor ability, nerve conduction, reflex and autonomic function Secondary endpoints included Norfolk QOL-DN quality of life score and exercise intensity (nis-w), disability (r-ods), walking speed (10 meter walking test), nutritional status (MBI) and autonomic nervous symptoms (compass-31) Exploratory endpoints included cardiac measurements in patients with baseline myocardial involvement, as well as measurements of skin amyloid burden and nerve fiber density in skin biopsies For mnis + 7 and Norfolk QOL-DN measurements, a lower score means better clinical results The results of the study were published in the New England Journal of medicine, 5 July 2018 The results showed that paisiran achieved excellent therapeutic effect, reaching the primary and all secondary end points of the study: compared with placebo, paisiran improved polyneuropathy, quality of life, ability of daily life activities, walking ability, nutritional status, autonomic nervous symptoms In addition, a cardiac subgroup analysis of patients with myocardial involvement (56% of the total number of study patients) showed that patisiran also showed significant improvement in cardiac structural and functional exploratory endpoints compared to placebo In terms of safety, the incidence and severity of adverse events were similar in the patisiran treatment group and placebo group The incidence of peripheral edema and infusion related reactions was higher in the patisiran treatment group, but it was usually mild to moderate Specific data: in the 18th month of treatment, compared with the placebo group, the Minis + 7 in the patisiran treatment group was significantly lower than the baseline (P < 0.00001), and the quality of life was significantly improved (P < 0.00001) Compared with the placebo group, the mean and median changes of NNIS + 7 injury score and quality of life score in the patisiran treatment group were negative, indicating the improvement of relative baseline in most patients and overall patients In addition, compared with placebo group, paisiran treatment group showed statistically significant difference in all 5 secondary endpoints (P < 0.001) The heart subgroup analysis showed that patisiran was associated with a significant improvement in cardiomyopathy compared to placebo In this study, the overall security of patisiran is encouraging The incidence of adverse events was similar in patisiran group and placebo group (AES: 96.6% vs 97.4%), and the incidence of serious adverse events was also similar (SAEs: 36.5% vs 40.3%) Onpattro is an intravenously administered RNAi drug that targets thyroxine delivery protein (TTR) Onpattro aims to target and silence specific messenger RNA (mRNA) and block the production of TTR protein, which may help to reduce deposition and promote the clearance of TTR amyloid protein in peripheral tissues and restore the function of these tissues Onpattro was approved by the US FDA in August 2018, and became the first RNAi drug approved for marketing in 20 years since the RNAi phenomenon was found This drug is used to treat polyneuropathy in adult patients with HTTR amyloidosis In addition, onpattro has also been approved for this indication in Canada and Japan, and for the treatment of stage 1 or stage 2 multiple neuropathy in adult patients with HTTR amyloidosis in the European Union and Switzerland HTTR is a progressive and life-threatening disease Onpattro solves the root cause of the disease by reducing the production of abnormal proteins that damage the whole body's nerves and organs The industry is also very optimistic about the business prospects of onpattro Evaluatepharma, a pharmaceutical market research firm, predicts that onpattro's sales will reach $1.308 billion in 2024 It is worth mentioning that in August last year, tegsedi (inotersen), an antisense RNA drug from Ionis, an American biopharmaceutical company, was approved by FDA for the treatment of stage 1 or stage 2 multiple neuropathy in adult patients with HTTR amyloidosis This approval makes tegsedi the first drug approved to treat hattr in the world Original source: Alnylam announcements filling for marketing authorization of onpattero ® (patisiran) in Brazil for the treatment of hereditary attr amloidosis with polyneuropathy