CDE priority review publicity page On April 3, 2017, the world's first deuterated drug, —Austedo™(deutetrabenazine), was approved by the US FDA for the treatment of abnormal involuntary movements caused by Huntington's chorea. Austedo™ is a small molecule oral inhibitor targeting VMAT-2 (Vesical Monoamine Transporter 2). Huntington's Disease is a rare autosomal dominant genetic disease, and there is no effective treatment at present. The specific mechanism is unknown, but it is considered to be related to its reversible monoamine depletion. In addition, this product has been approved by FDA for delayed dyskinesia in adults. In 2018, Austedo™'s global revenue was 204 million US dollars; In the first three quarters of 2019, sales in North America were 275 million US dollars; The global performance in FY 2019 was USD 412 million. Austedo™ was first developed by Auspex Pharmaceuticals, and Teva acquired it in 2015 with a huge amount of USD 3.5 billion. The two sides first reached cooperation in 2010. Austedo™ is a deuterated drug of Huntington drug Xenazine(Tetrabenazine), and the synthetic route refers to US2014066740.
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Structural formula of butylenazine and SD-809 (deuterated butylenazine)
Deuterium, also known as heavy hydrogen, is a stable isotope of hydrogen atom, and its element symbol is d. After replacing hydrogen with deuterium, the metabolic site may be closed, so that the drug half-life is prolonged and the pharmacokinetic characteristics are obviously improved, while the pharmacological activity is not affected (the shape difference between H and D is small).
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Domestic enterprises developing deuterated drugs include Zejing Bio, Chengdu Haichuang Pharmaceutical, Tongyuankang, Zhengda Tianqing and so on.
Overseas enterprises developing deuterated drugs include BMS, Concert Pharma, Aclaris Therapeutics, Alkeus Pharma, DeuteRx, Euclises, Vertex and so on.
CDE's viewpoint on the urgent need of overseas new drugs in clinic; Kong Fanpu, director of CDE, issued a document entitled "Progress of Drug Evaluation Reform" at the end of 2019, saying that overseas new drugs are urgently needed clinically, and there are still some problems in this work: ① Some multinational companies have their own business plans for the global listing of their products, and the time for their listing and registration in China may be delayed compared with Europe, the United States and Japan. ② It takes a certain period to prepare the registration application materials. ③ Some overseas enterprises have insufficient motivation to register and list in China. In the next step, CDE will further strengthen communication and actively guide enterprises to declare. For the varieties that have been listed in the list of urgently needed overseas new drugs, after accepting their registration applications, they will be directly included in the special channel to speed up the review and simplify the review links and processes.