The first deuterium drug in the world! Austedo (deutetrabenazine) failed to register stage II / III clinical treatment of Tourette's syndrome!

February 21, 2020 / BIOON / -- Teva Pharma recently released the results of phase II / III artists 1 and phase III artists 2 tests These two trials were conducted in pediatric patients with moderate to severe Tourette syndrome (TS), and the results showed that austedo (detrabenazine, tablet) failed to reach the primary end point of reducing motor and vocal tic TiC (evaluated by Yale comprehensive tic severity scale - Total tic score [ygtss-tts]) compared with placebo Among the data received this week, the most frequently reported adverse events in the arts 1 and 2 studies were headache, drowsiness and fatigue In these patients, no new safety signals were found that were inconsistent with the known costedo safety profile Tourette syndrome (TS) is a kind of neurodevelopmental disorder The onset age is before 18 years old TS is characterized by motor and vocal convulsions lasting for more than one year The symptoms of TS usually first appear in the early childhood, and the most serious symptoms appear around the age of 10 Most of TS patients have improved symptoms in late adolescence and adulthood Dr hafrun fridriksdottir, executive vice president of global R & D of TIWA, said: "the results of these trials are very disappointing, especially considering the significant unmet medical needs of the pediatric population with Tourette's syndrome We are currently assessing the next steps of the drug program, and we are particularly grateful to the investigators, patients and families involved in these studies " Austedo: the first deuterium drug in the world, austedo, is a small molecule oral inhibitor targeting vesicular monoamine transporter 2 (VMAT2) VMAT2 is responsible for regulating the levels of dopamine, 5-hydroxytryptamine, adrenaline, noradrenaline and other chemicals in the brain Deuteratetrabenazine is a deuterium drug of tetrabenzazine, which has been listed as the treatment drug of Huntington's disease After deuterium, the pharmacokinetic characteristics were improved, and the half-life was significantly prolonged, so that a lower therapeutic dose could be used Austedo is the first deuterium drug approved in the world In the United States, austedo was approved by the FDA in April 2017 for the treatment of Huntington's disease-related chorea In August 2017, the FDA approved a new indication of austedo for the treatment of adult tardive dyskinesia TIWA: a pioneer in the field of deuterization technology deuterium (d) element is very rich in nature, and can form stable molecular bonds with other elements In an adult, the average content of D is about 2G Although D and H are basically the same in size and shape, there is also a fundamental difference between D and h, that is, D contains an additional neutron As a result, the chemical bond between D and C is more stable than that between H and C In general, the stability of d-c bond is 6-9 times higher than that of H-C bond, which has a very important impact on drug development, because drug metabolism often involves the breaking of H-C bond The traditional method of drug discovery takes a long time and has a high failure rate The deuterium chemical method, usually based on the drugs already on the market, has higher development efficiency and lower cost Deuterization (deuterium substitution) can enhance some properties of drugs: due to the formation of more stable chemical bond between D and C, in some cases, it can change the metabolism of drugs, including improving the stability of metabolism, reducing the formation of toxic metabolites, increasing the formation of required active metabolites, or a combination of these effects Compared with the corresponding non deuterium analogues, deuterium compounds have longer half-life in vivo and increased system exposure, which may bring therapeutic benefits, such as increased safety, effectiveness, tolerance and convenience In general, deuterated compounds are expected to retain biochemical potency and selectivity similar to their hydrogenated analogues The effect of deuterium substitution on metabolic properties is highly dependent on the specific molecular position of d-substituted H However, the metabolic effects of deuterium substitution, if any, are unpredictable, even in compounds with similar chemical structures At present, a number of pharmaceutical companies are developing deuterium drugs for existing drugs For example, concert has developed a new product ctp-543 by using deuterium chemical technology to inhibit ruxolitinib, a Jak1 / JAK2 inhibitor, and has achieved strong curative effect in the treatment of alopecia areata Ruxolitinib has been approved for sale in the United States under the brand name jakafi for the treatment of various blood diseases The deuterium chemical modification of ruxolitinib can change the pharmacokinetics of ruxolitinib in human body, so as to enhance its application in the treatment of alopecia areata Origin of the original text: 1 Teva announcements registration trials of deuterium benzine in pediatric patients with Tourette complex did not meet the primary endpoint 2 Deuterium chemistry technology