Will PD-1 / PD-L1 be approved in limited quantities? Breakthrough therapy is not approved for two main reasons.

As in previous years, this year is still Minister Yang Zhimin led the CDE chemical clinical department and pharmaceutical industry, medical colleagues report results, exchange ideas, answer questions.
The content of this special report mainly includes the following 6 aspects: CDE chemicals clinical first minister Yang Zhimin reported "2020 China anti-tumor new drug review report" CDE drug clinical a senior reviewer Zhang Hong "anti-tumor new drug technical guidelines interpretation" CDE chemical clinical first senior reviewer Xia Lin "anti-tumor immunotherapy research and development review consideration" CDE drug clinical first senior reviewer Zhou Ming "Joint Development review of anti-tumor drugs" CDE drug clinical senior reviewer Yu Limin "breakthrough determination to accelerate the development of new anti-tumor drugs" CDE statistics and clinical pharmacology senior reviewer Pan Jianhong "adaptive design to accelerate the development of new anti-tumor drugs" Yang Zhimin from the review work, review considerations and bottlenecks encountered (challenges) introduced the 2020 China Anti-Tumor Innovation Drug Review Report.
as of September 10, 2020, CDE had approved a total of 19 cancer drugs.
" approvals is not important, it is important that many cancer drugs approved this year are 'first'.
"This includes the first ADC, the first PD-L1 inhibitor for small cell lung cancer, the first PD-1 inhibitor for stomach cancer, and the first monobial-like drug for quercetoju..."Compared with the same period in 2019, the number of new anti-tumor drugs approved for market in 2020, the proportion of priority reviews and the proportion of domestic varieties all showed an upward trend, but the approval time and average time were extended by 4 to 5 months.
Yang Zhimin explained, "The reasons for the extension of the review time, there are three main points: due to the outbreak led to verification and inspection procedures, some of the project research work is not sufficient, the quality of the declaration is not high leading to multiple rounds of supplements, pharmaceutical changes during the research and development related research work is insufficient."
" Yang Zhimin also mentioned that in the anti-tumor drug communication and communication work, this year's pre-market exchange rate increased significantly, indicating that the previous years of research and development of cancer drugs are flowering results.
CDE reviews innovative cancer drugs, it still mainly considers such factors as overall planning for research and development, new innovative research design, precision population, one-arm trials, and combined therapy.
she warned that key pharmacological data should not be ignored and encouraged the introduction of young patients into the group to promote access to medicines for children.
PD-1 / PD-L1 so much, will it be approved in limited quantities? In recent years, the number of single-drug clinical trials conducted in PD-1/PD-L1 single-drug domestic has gradually slowed down, while the number of combined therapy clinical trials has shown a blowout growth.
it is worth mentioning that PD-1/PD-L1 monoantigens in China to carry out clinical research target adaptation gradually differentiated, the maximum adaptive disorder is still non-small cell lung cancer (NSCLC).
It is interesting that, in the special discussion, Professor Wu Yilong asked the reviewer, "There are so many projects in China to carry out PD-1/L1 clinical trial research, when the approved PD-1/L1 reaches a certain number, will CDE set a number of approvals from a regulatory perspective?" And then the declared items are no longer approved? "On the one hand, the early approval of PD-1 is mostly conditional approval, if the subsequent product does not show a significant increase in efficacy, in principle, the same indication does not take conditional approval; The standard of PD-1 approved first is mostly single-drug comparative chemotherapy, and as more and more domestic PD-1 is approved, the treatment standard of NSCLC should be raised to PD-1 plus chemotherapy, the clinically designed control standard will no longer be controlled chemotherapy, but with PD-1 plus chemotherapy.
, CDE does not set a specific number of PD-1/PD-L1 approvals, but limits subsequent clinical developers by raising the review threshold.
so hot as Combo's development, how do you choose a co-drug? Anti-tumor drugs are the hot spot of innovative drug research and development at home and abroad, and new targets, new mechanisms and new structures are emerging.
to overcome drug resistance and pursue greater clinical benefits, joint development has become one of the hottest directions in cancer research.
joint treatment has become a hot spot in the development of cancer drugs in 2020, and innovative joint models such as targeting joint and immune union have gradually become a development normal.
To this phenomenon, the CDE internal joked that the original intention of the current joint project of the industry has become "others, I will link;
of a reasonable drug will improve clinical benefits, inappropriate co-use will increase adverse reactions and pharmacoeconomic toxicity.
To this end, NMPA CDE released the Technical Guidelines for Clinical Trials of Anti-Tumor Drug Joint Therapy in July this year, which suggest that the industry needs to consider when new anti-tumor drugs enter the Joint Development Options Partnership (CP): rational basis, single-drug data, and exploratory trial design.
in CDE teacher's view, the joint mechanism should be based on science, the choice of joint partner (CP) should give priority to strong union, but also need to consider changes in clinical practice.
specific measures include exploratory testing, obtaining reasonable basis, suitable population, optimal dose, biomarkers, risk control, analysis of causes, etc., and conducting corroroitative tests to confirm the rationality and clinical advantages of joint therapy.
breakthrough therapy not approved, what's the reason? To encourage innovation and meet clinically urgent needs, NMPA has established four accelerated channels for breakthrough therapeutic drug procedures, conditional approval procedures, priority review approval procedures, and special approval procedures.
CDE teacher mentioned that the significance of the implementation of breakthrough therapeutic drug work procedures lies in the early clinical data to explore the advantages of products, focus on multi-resource research and development, shorten the advantages of product development cycle, improve the number of successful approvals, reduce the number of new molecular entities stop before the clinic, so that patients get better treatment at an early stage.
with the implementation of the new Measures for the Administration of Drug Registration on July 1 this year, breakthrough therapeutic drug procedures have also arrived on schedule.
as of September 10, 2020, CDE had received 87 breakthrough treatment applications, including 64 oncology products, and all four applications that had been announced had been formally incorporated.
that some of the projects that have not been approved for breakthrough therapy have not been approved for both regulatory and data reasons.
regulatory reasons include: 1) overseas approved allergies (non-new drugs/improved new drugs); 2) Pre NDA communication has been completed and agreed to submit NDA; 3) the same application contains multiple allergies; data reasons include: 1) sample size is too small / data is not robust; 2) the efficacy is not outstanding; 3) population definition is not clear; 4) no clinical research data.
In addition to the above industry concerns, CDE teachers also shared how to accelerate the development of new anti-tumor drugs through adaptive design, including group sequential design, sample size revaluation, adaptive seamless dose selection design, adaptive rich design and adaptive master program design, and suggested that clinical endpoint selection of cancer immunotherapy drugs should be based on practical comprehensive considerations, and encouraged communication with regulatory agencies to select the advantages of the evaluation indicators as the main research endpoint.
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