CDE first innovative drug approval "privilege" upon completion of phase II clinical approval

"Privilege" of approval of innovative drugs In 2009, China promulgated and implemented the regulations on the administration of special examination and approval of new drug registration According to the general principles of "early intervention, priority review, multi-channel communication and exchange, dynamic supplementary information" of new drug registration applications for special examination and approval, the regulations specify the special examination and approval conditions, procedures and requirements for new drug registration, and clarify the rights of applicants in the process of special examination and approval of new drug registration Benefits and obligations Although there is a certain gap with the implementation of FDA special review channel, domestic CDE has gradually moved closer to foreign laws and regulations in accelerating the approval of innovative drugs It's a good thing to speed up the process of new drug listing in 10 months, but it's not easy to pass a special fast approval path in the process of new drug development, which requires many conditions At the same time, the approved listing is not the end of new drug development The enterprise should also complete the clinical trials with due diligence, verify the safety and effectiveness of drugs after listing, and ensure the quality is controllable Bao Jun said that there are three preconditions for the rapid approval of drugs: for the treatment of serious or fatal diseases, obviously effective compared with the existing treatment, and the existing treatment can not meet the treatment or diagnosis "The key factors to be approved also include: having alternative clinical indicators that can reasonably predict the clinical effectiveness, having to continue to verify the clinical effectiveness of the drug, having generally started the validation test after the drug is put on the market, and having the applicant complete the test with due diligence." It should be noted that if the post marketing validation test fails to prove the clinical effectiveness, or the applicant fails to fulfill the test due diligence, FDA can withdraw the approval after public discussion According to statistics, since the implementation of FDA in 1992, 53 blood disease and cancer products, including 70 new indications, have received accelerated approval, of which 50% of the efficacy has been confirmed and officially approved, 10% of the efficacy has failed to be confirmed and withdrawn from the market, and 40% are in post market trials or in FDA review The real significance of rapid approval in China is just in its infancy When accelerating the approval, the regulatory authorities need to weigh the risks of accelerating the drug market and increasing uncertainties For enterprises, the key to reduce the risk of invalid drug marketing is to prepare post marketing research plan with due diligence, effort and as early as possible, so as to form a complete drug R & D plan applying for accelerated approval "CDE is very happy to communicate with new drug developers now As long as the drugs that really meet the clinical needs can maintain good communication, under the current drug approval system framework, it can be achieved to accelerate the progress for 10 months." Said Dr Lu Xianping, President and chief scientific officer of Shenzhen micro core Biotechnology Co., Ltd It is understood that the fast approval channels of FDA are divided into four types: fast track, breakthrough therapies, priority review and accelerated approval, which are all drugs for serious or fatal diseases Fundamentally speaking, the first three belong to qualification recognition and may not be approved for listing However, wheel review enables researchers to submit application materials in different times according to pre clinical, clinical and production application materials to accelerate the application efficiency; and accelerated approval belongs to the approval way, which can ensure the acceleration of listing process "The purpose of establishing an accelerated approval channel for drugs by FDA is to get new drugs on the market as soon as possible, so the idea of FDA is to participate in the whole process." According to Dr Gong Zhaolong, the former senior drug review expert of FDA and chief executive officer of mindI pharmaceutical, the FDA has started to intervene before the application of new drugs As long as the preclinical and clinical data can prove that it is possible to meet the medical needs that the existing therapies cannot meet, it can enter the green channel The threshold of breakthrough therapy is relatively high, and clinical data is needed to show that its clinical effect may be significantly better than the existing therapy; accelerated approval is to replace the clinical end point with an alternative end point that can predict clinical benefits, which is approved first and then verified If the clinical effect is verified after being put on the market, FDA will maintain the original approval and the new drug will be "positive" Gong pointed out that the main consideration of accelerated approval is actually to make drugs without treatment available on the market ahead of time, so as to save the lives of patients without medicine Chidamide, epsilon/ Epidaza) is a new subtype selective histone deacetylase inhibitor independently developed by microchip biology, which has a new chemical structure and obtained global patent authorization It is a new epigenetic regulator with a new mechanism of action and a new targeted anti-tumor drug In February 2013, it was submitted to SFDA for adapting to recurrent or refractory peripheral T-cell lymphoma (PTCL) Application for new drug certificate (NDA) and marketing approval (MAA) of the disease Sidabamide is the first Chinese chemical original new drug approved by FDA to conduct clinical research in the United States while conducting a number of tumor clinical trials in China, and has completed the phase I clinical trial research in the United States The main target of sidabamide is to target the first HDAC subtype which is highly related to the occurrence and development of tumor By inhibiting specific HDAC subtypes and the resulting chromatin remodeling and gene transcription regulation (epigenetic regulation), cedarbamine can inhibit the cell cycle of lymphoid and blood tumors and induce tumor cell apoptosis; induce and enhance the tumor killing effect mediated by natural killer cells (NK) and antigen specific cytotoxic T cells (CTL) and inhibit tumor pathological groups The inflammatory response of tissue can not only directly contribute to the therapeutic effect of circulating tumor cells and local lesions in T-lymphoma, but also can be used to induce and enhance the overall regulatory activity of anti-tumor cell immunity against other types of tumor In addition, through epigenetic regulation mechanism, cedarbamide can induce tumor stem cell differentiation and reverse epithelial mesenchymal phenotype transformation (EMT) of tumor cells, so as to restore the sensitivity of drug-resistant tumor cells to platinum, paclitaxel and topoisomerase II inhibitors and inhibit tumor metastasis and recurrence Use At present, the clinical research on the combination of cidabamide and chemotherapy drugs in the treatment of lung cancer and many other tumor clinical research are in progress Peripheral T-lymphomas (PTCL) belong to the category of rare diseases There are at least 18 different pathological subtypes, which are very complex At present, there is a lack of recommended treatment methods of standard drugs in clinic The response rate to conventional chemotherapy is low and easy to relapse The 5-year overall survival rate is only about 25% Folotyn, the world's first new drug for PTCL treatment (pralatrexat, allos therapeuties Inc., intravenous drug use) was approved by FDA in 2009 The second new drug, istodax (romidepsin, celgene company, intravenous drug) was approved by FDA in 2011 When the two new drugs will be launched in China is far away The results of phase II clinical trial of sidabamide showed that the objective remission rate of the main efficacy index of single drug treatment application was 28%, which reached the predetermined goal proposed by SFDA drug review center (CDE) (i.e., referring to the objective remission rate of 26.5% and istodax of folotyn approved by FDA in the United States 25%); the three-month sustained remission rate was 24%, significantly higher than that of folotyn's 12%; it is worth noting that the distribution of various subtypes of PTCL in Chinese population may be significantly different from that in European and American population For example, NK / T cell lymphoma has a poor prognosis, and few patients can survive for more than 5 years The proportion of patients with NK / T-cell lymphoma subtype treated with xidabamide was 20% (much higher than 2% of pralatrexate and 1% of romidepsin), which showed the epidemiological characteristics of this subtype in Chinese PTCL patients However, even if there is such a subtype difference, the objective remission rate of sidabamide is still comparable with that of two internationally listed drugs In addition, the safety of xidaban is better than that of the same kind of drugs in the world The main adverse reactions of xidaban were hematotoxicity, gastrointestinal toxicity and asthenia Blood toxicity can be found by blood routine test, and can be improved after corresponding symptomatic treatment The toxicity and weakness of digestive tract are mostly mild and moderate, which can be improved after symptomatic treatment without affecting the continuous use of drugs Therefore, the adverse reactions caused by xidaban are controllable Sidabamide is an oral drug, which has a more convenient clinical medication mode and better compliance It is obviously superior to pralatrexate and romidepsin The results of comprehensive efficacy evaluation and safety analysis of clinical studies suggest that sidabamide may have at least equal or better efficacy and better safety tolerance compared with the two drugs already on the market in the world Xidaban is expected to become the first Chinese drug for the treatment of PTCL and the third new drug approved for the treatment of PTCL in the world For more information, please go to the website of epidaza products (link: http://www.epidaza.com)