Teva Pharma recently announced that the China National Drug Administration (NMPA) has approved Austedo (common name: deutetrabenazine) for the treatment of adult patients with Huntington's disease (HD)-related chorea and tardive movement disorders (TD). The drug's marketing application was previously included in the priority review by the NMPA Drug Evaluation Center (CDE). It is worth mentioning that Austedo is the world's first approved deuterated drug, and China is the second country after the United States to approve Austedo.
As part of the rapid review process, NMPA included Austedo on the list of "Clinically Urgently Needed Overseas New Drugs (First Batch)" and gave priority review, and finally completed the approval process within 4 months to benefit Chinese patients. This is the second approval and expected launch of Teva's specialty medicine in China following the recent launch of Treanda (common name: bendamustine). Teva will independently commercialize this drug in China.
Gianfranco Nazzi, Executive Vice President of Teva International Markets, said: "The approval of Austedo in China is an exciting milestone for Teva. We are fulfilling our mission to improve the lives of patients by providing a new treatment plan. We look forward to providing Chinese patients with more essential medicines in our product portfolio, and to promote organic growth and expand our presence in this important market."
Huntington's disease (HD) is a rare and fatal neurodegenerative disease with a total prevalence of 0.40/100,000 in Asia and an average age of onset of 40 years. Dance disease is one of the most significant physical manifestations of the disease, occurring in about 90% of patients.
Tardive dyskinesia (TD) is a movement disorder characterized by repetitive and uncontrollable movements of the tongue, lips, face, trunk and limbs. This is a disease that is often debilitating and affects about 500,000 people in the United States, usually due to the widely used drug or gastrointestinal metoclopramide (metoclopramide), which is widely used in the treatment of mental disorders such as schizophrenia and bipolar disorder ).
In China, the prevalence of TD among schizophrenic patients who have been taking antipsychotic drugs for a long time is 33.7%, which may be caused by certain drugs for the treatment of mental health, which means that up to one third of schizophrenia The patient may have TD. The disease not only affects the patient's compliance with treatment, but also affects the patient's quality of life and social function. Austedo is China's first approved treatment for TD.
Austedo: the world's first deuterated drug
Austedo's active pharmaceutical ingredient is deutetrabenazine (deuterated tetrabenazine), a small molecule oral inhibitor targeting vesicle monoamine transporter 2 (VMAT2), which regulates the Dopamine, serotonin, epinephrine, norepinephrine and other chemical levels. Deutetrabenazine is a deuterated drug for tetrabenazine, a treatment drug for Huntington's disease. After deuteration, the pharmacokinetic characteristics are improved, and the half-life is significantly extended, so that lower therapeutic doses can be used.
Austedo is the first deuterated drug approved globally. In the United States, Austedo received FDA approval in April 2017 for the treatment of chorea associated with Huntington's disease. In August 2017, the FDA approved a new indication for Austedo for the treatment of delayed-onset dyskinesia in adults.
Teva: a pioneer in the field of deuteration
The deuterium (D) element is very abundant 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 hydrogen (H) are basically the same in size and shape of atoms, there is a fundamental difference between D and H, that is, D contains an extra neutron. As a result, the chemical bond formed by D and carbon (C) is more stable than the chemical bond formed by H and C. In general, the stability of D-C chemical bonds is 6-9 times higher than that of H-C chemical bonds, which has a very important impact on drug development, because drug metabolism often involves the breaking of H-C chemical bonds.
Traditional drug discovery methods take a long time and have a high failure rate. The deuterium chemistry method is usually based on the drugs already on the market. In contrast, the development efficiency will be higher and the cost will be lower. The use of deuteration (deuterium substitution) can enhance certain properties of drugs: D and C can form a more stable chemical bond. In some cases, D can change the metabolism of drugs, including improving metabolic stability and reducing toxic metabolites. Formation, increase the formation of the desired active metabolite, or a combination of these effects. Compared with the corresponding non-deuterated analogues, deuterated compounds have a longer half-life in the body and increased system exposure. These properties may bring therapeutic benefits, such as improved safety, effectiveness, tolerability and convenience.
In general, deuterated compounds are expected to retain biochemical efficacy and selectivity similar to their hydrogenated analogs. The effect of deuterium substitution on metabolic properties is highly dependent on the specific molecular position where D replaces H. However, the metabolic effect of deuterium substitution (if any) is unpredictable, even in compounds with similar chemical structures.
At present, many pharmaceutical companies are developing deuterated drugs that are currently on the market. For example, Concert Company has developed a new product CTP-543 with JAX1/JAK2 inhibitor ruxolitinib using deuterium chemical technology, which has achieved strong efficacy 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 its human pharmacokinetics, thereby enhancing its use as a treatment for alopecia areata.