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    Home > Active Ingredient News > Drugs Articles > In-depth analysis of overseas strategy, every innovative drug needs "tailor-made" clinical trials!

    In-depth analysis of overseas strategy, every innovative drug needs "tailor-made" clinical trials!

    • Last Update: 2022-10-13
    • Source: Internet
    • Author: User
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    The unforgettable year of 2022 is more than halfway through, and we who are in the wave of change of the times can feel more and more clearly the changes in the industry pattern and the world environment of
    the pharmaceutical industry.
    China's innovative drug power has risen rapidly in the past few years, filling the domestic market gap, and even the surplus of homogeneous new drugs brought about by "saturation research and development" has led to a serious phenomenon of
    internal volume.

    Going to sea has become one of the important ways to digest excessive supply, alleviate bad competition, and let the innovative forces develop healthily, and the simultaneous listing of new drugs at home and abroad has gradually become the norm
    .
    According to the incomplete statistics of the drug era, as of August 31, 2022, there are at least 123 Chinese new drug-related enterprises that have "officially announced" the progress of going overseas
    .
    Therefore, it should not be too much
    to describe the current situation of China's pharmaceutical industry as "the right time to go to sea".
    The success of going to sea has become a "life event"
    for the development and even survival of some pharmaceutical companies.
    However, it is not advisable to go to sea blindly with only a heart of blood, and it is necessary to plan
    to go to sea.
    In order to help many pharmaceutical companies sort out their overseas strategies and throw bricks and stones, this article will explore the content of 4 aspects:

    1.
    The challenges that may be faced when going to sea

    2.
    From the comparison of Chinese and American regulations, we can see the sea opportunities

    3.
    "Accurate project establishment"
    of project establishment strategy.

    4.
    "Tailor-made" sea plan for drugs

    Going to sea is not easy, be prepared for "warm-up"

    Going to sea is not easy, be prepared for "warm-up"

    Going to sea is still a bumpy road
    with few references and thorns for most Chinese innovative pharmaceutical companies.
    Stage victories such as signing an authorization cooperation with MNC can hardly hide the reality
    of the overall setback of Chinese pharmaceutical companies going to sea.
    In the various stages before the overseas listing of products, the "fledgling" Chinese "back wave" are more or less facing various problems and challenges, and the incidents of Chinese pharmaceutical companies going to sea and setbacks have also occurred
    from time to time.
    Drug going to sea is a complicated project, and designing a successful drug molecule is only the first step
    in the long march.
    On the way to the sea, pharmaceutical companies will also face many challenges
    .

    At the project establishment stage, it is necessary to consider the competitive landscape, regulatory policies and optimal listing path of the product;

    Preparation in the clinical phase, from trial protocol design and proof-of-concept to local patient recruitment and supply chain assurance;

    In terms of capital, resources in the international capital market are limited, and the financing environment is very complex, which requires adequate coping strategies
    .

    The challenges of going to sea are varied, and one of the core reasons is "strangeness"
    .
    In the face of these difficulties and challenges, international clinical CRO companies are more experienced because of their global operations, perennial contact with clinical centers around the world, and familiarity with local regulatory processes; On the other hand, years of clinical trial design and execution have also made them experience challenges far beyond those of ordinary pharmaceutical companies, making it form a unique and effective methodology
    .

    Is it true that single-country trial data cannot be approved by the FDA?

    Is it true that single-country trial data cannot be approved by the FDA?

    In the first half of this year, there were several domestic innovative drugs that have attracted the attention of the industry, among which whether a single Chinese data can be recognized by the FDA has become a hot topic
    .
    In the view of Dr.
    Amy Mckee, chief medical officer of Jingding Pharma and global head of the Center of Oncology Excellence, although the key registration studies of these products were completed only in China and received a complete reply letter from the FDA that did not approve it, the reason for the failure could not be attributed to the issue
    of "single China data".
    In fact, according to publicly available information, the reasons for the rejection of these products by the FDA are different in some details
    .

    Dr.
    Amy Mckee, Chief Medical Officer and Global Head of the Center of Oncology Excellence at Jingding Pharmaceutical

    Dr.
    Amy Mckee, Chief Medical Officer and Global Head of the Center of Oncology Excellence at Jingding, has 11 years of experience with the FDA, is the Deputy Director of the Center of Excellence for Oncology and Deputy Director of Oversight of CDER OHOP, and has served as a Product Signing Representative
    for the Office of Hematology and Oncology Products (OHOP) of the Center for Drug Evaluation and Research (CDER).
    She has managed four FDA divisions responsible for conducting scientific reviews and evaluations of hematology and oncology drugs and biologics to ensure that products meet CDER regulations
    .

    Dr.
    Amy Mckee

    Based on some public information, Amy analyzed these detailed problems, mainly from five aspects: 1.
    Product quality and pharmaceutical research issues
    .
    2.
    On-site verification issues (such as the FDA cannot conduct clinical trials or production on-site verification due to the new crown epidemic
    ).
    3.
    Clinical trial design problems
    .
    4.
    Compliance issues, including details
    such as GCP compliance, data integrity and patient informed consent.
    5.
    Clinical needs
    .
    The urgency of clinical needs affects the flexibility of the FDA in approving drugs, and the more urgently needed indications, the easier it is to be "forgiven"
    for other flaws.

    It is worth mentioning that clinical design issues can be divided into three parts
    .
    One is the choice of endpoints of clinical trials, such as when other products with the same indication have selected OS as the primary endpoint, and the declared products have not selected OS as the primary endpoint; The second is the control group, which did not select the current standard treatment regimen in the United States according to the US Pro Practice; The third is the subject, can not well represent the demographic characteristics of the American patient, the population here is not only ethnic, but also includes the subject's age, gender and other characteristics, such as: the trial patients are smaller than the average age of the American patients, or the clinical trial is mainly enrolled in male patients, and the drug targets the disease in the United States The incidence rate of men and women is equal
    .

    Such a trial design also does not support the risk-benefit assessment of the drug for use in the
    US population.
    Amy said that sometimes pharmaceutical companies have too many screening criteria for subjects, resulting in the final test population being far from
    the actual clinical drug population.
    In particular, the FDA updated the latest edition of the Guidelines for Increasing Diversity in Clinical Trials in 2020 to allow enrolled clinical trial patients to more accurately reflect the affected population
    in the United States using the therapy.
    In addition, since the FDA adopts the regulatory framework of ICH E17, some of the ICH E17 guidelines can also be referenced, and it is worth noting that regulatory agencies around the world are increasingly concerned about subject population and racial adaptability
    .

    It is worth noting that regulators everywhere are paying more and more attention to the subject population and racial adaptability
    .

    This can also be seen
    in Chinese regulations.
    In fact, if we understand Chinese regulations more deeply, we will find that they are similar
    to the regulatory regulations of various countries.
    As Li Yajie, vice president of R&D strategic consulting technology in the Asia-Pacific region of Jingding Pharmaceutical, said to the pharmaceutical era: "The products of Chinese local enterprises go out and foreign products come in, in fact, they follow the same logic
    .
    By strengthening the understanding of Chinese regulations, it is possible to further clarify the optimal strategy
    suitable for pharmaceutical companies to go global.

    Li Yajie, Vice President of R&D Strategic Consulting Technology, Asia Pacific Region, Jingding Pharmaceutical

    Yajie Li, Vice President of R&D Strategic Consulting Technology for Jingding Pharma Asia Pacific, has more than 10 years of experience in the pharmaceutical industry and also served as a senior clinical reviewer
    at the Drug Evaluation Center (CDE) of the former CFDA (now NMPA) for nine years.

    Li Yajie

    In order to give Chinese patients access to the world's most advanced innovative therapies, the State Food and Drug Administration has issued a number of documents or guidelines since 2015 to accelerate the internationalization process
    .
    The most important of these is the Clinical Technical Requirements for Domestically Unlisted Drugs Listed Abroad issued in October 2020
    .
    Li Yajie told Yaoshi that although the name of the document is "Overseas Listed Drugs Not Listed in China", it actually applies to all drugs
    that plan to use global clinical trial data to register and market in China.

    For drugs that use global data to support the declaration in China, the review logic of the regulatory authorities is to evaluate
    the clinical needs of the declared drugs in China, and the safety, efficacy and racial sensitivity reflected in the clinical trial data of the drugs.
    When conducting race-sensitivity assessments, regulators pay particular attention to the characteristics of the disease in China, whether clinical practice is different, and whether Chinese clinical trial data differs from other races
    .
    Finally, regulators will make regulatory decisions
    based on the results of the above assessment for the benefit/risk ratio of Chinese patients.

    In simple terms: in the case of national data, and the safety and efficacy of the drug have been proven, if there is no racial sensitivity - to be approved for marketing; If there is no national data, but there is no concern about racial sensitivity, and the drug is urgently needed clinically - conditional approval for marketing may be considered; If it is not clinically needed and there is no racial sensitivity data, it is necessary to carry out corresponding PK, PD, and safety effectiveness studies
    in China.
    Li Yajie concluded: "We can simply divide the drug research and development strategy that plans to be declared globally as: global synchronous development path; Country-specific bridging paths; Separate development paths for a country; Other (e.
    g.
    exemption paths), etc
    .

    Chinese local enterprises going out, or foreign companies coming in, are generally based on the global data of drugs or the current stage of research and development, as well as the existing data to analyze which path is better, so the logic is the same
    .
    " After understanding the scale and flexible space for regulatory agencies to approve drugs, the optimal strategy for project establishment is more clear
    .

    "Precision medicine" for pharmaceutical companies - precision project establishment

    "Precision medicine" for pharmaceutical companies - precision project establishment

    Project initiation is fundamental
    .
    The so-called smart woman is difficult to cook without rice, and choosing the right project for development can not only obtain a large operating space in the subsequent stage of going to sea, but also allow the company to obtain the greatest commercial value
    .
    Mr.
    Zheng Zichuan, Vice President of Health Advances, a strategic consulting company under Jingding, presented a set of data to the pharmaceutical era:

    Mr.
    Zheng Zichuan, Vice President of Health Advances, a strategy consulting company under Jingding

    According to the Pharmaprojects database, after classifying the new drug projects in the clinical stage of pharmaceutical companies in various countries in 2022 by key treatment areas, we will find that the most crowded tracks in China, the United States, Europe and Japan are all in the field of oncology, accounting for more than 30% of new drugs under research in this field, of which 42% in the United States and a staggering 58%
    in China.
    This also aptly reflects the current situation
    of Chinese pharmaceutical companies gathering to develop popular anti-tumor therapies.

    Gary Cheng, head of Health Advances' Hong Kong office, has extensive expertise
    in oncology and cardiovascular disease drugs, as well as bedside testing in the diagnostic field.
    During his 14 years at Novartis, he successfully brought a major oncology drug to the global market
    .
    During his time at BD, Gary explored more than 50 acquisition, licensing and partnership targets in China, Japan, Southeast Asia and India, and led Carefusion's integration efforts
    in Greater Asia.
    Primarily responsible for working with pharmaceutical companies, biotechnology companies, medical technology companies and private equity firms
    .

    Gary Cheng

    The big gap between China and the United States, Europe and Japan is in the gastrointestinal/metabolic and central nervous system fields
    .
    In the field of gastrointestinal/metabolic medicine, Chinese pharmaceutical companies accounted for 6% of new drugs under research, and 9%, 10% and 11% in the United States, Europe and Japan, respectively; The gap in the central nervous system sector is even greater, with figures for China at just 5 percent, the United States at 11 percent, Europe and Japan at 14 percent and Japan at 17 percent – close to or more than three times as many as
    China's.
    Compared with pharmaceutical companies in developed markets, the gastrointestinal/metabolic and central nervous systems fields are currently areas that Chinese pharmaceutical companies are relatively unconcerned about, and there are also certain urgent needs in the clinic, and there may be more opportunities
    .
    Zheng Zichuan also told the pharmaceutical era that there is no definite formula for setting up a project, and it is important to establish a set of its own screening criteria
    according to the company's situation, such as financial status, allocation of talent resources, and advantages (development or commercialization).

    The central nervous system field in the gastrointestinal / metabolic field

    To some extent, this is also the "precision medicine" of pharmaceutical companies - that is, accurate project
    approval.
    The screening criteria should include: evaluation of the development path of the drug, which involves the duration of clinical trials and the difficulty of patient recruitment; Market assessment, i.
    e.
    whether the indication corresponds to an unmet clinical need; Likelihood of technical success, drug delivery system; Choose first-in-class or best-in-class, me too or me better; Whether there is the possibility
    of cooperative development.
    Because the standard contains many entries, it is difficult to find a fully satisfied drug, so it is also necessary to set scorecards or rankings for the corresponding entries based on science and data to conduct a comprehensive evaluation
    .

    To some extent, this is also the "precision medicine" of pharmaceutical companies - that is, accurate project
    approval.

    After the initial screening using the filter entries, an in-depth evaluation is also conducted, and KOLs are collected feedback on drug and clinical data based on the company's treatment paradigm, and SWOT analysis
    is performed based on the competitive landscape and the owner's assets.
    All of the above can be assisted
    by Jingding Pharma and Health Advances.
    When it comes to projects going to sea, it is very necessary to consider whether to cooperate, Zheng Zichuan introduced three forms of going to sea, which are summarized in the pharmaceutical era as: independent going to sea, joining hands to go to sea, and borrowing ships to go to sea
    .

    Because China's innovative drugs are in their infancy at present, the use of external forces is the preferred strategy for many biotechnology companies, and the cooperation of a product may last for many years or even more than 10 years, therefore, the choice of partners may not only look at the fame of MNC, or see who bids high, but also have a certain strategy
    .
    In addition to matching the company's goals and needs, the selection of partners is also important, which is easy to overlook
    .
    Zheng Zichuan emphasized: "The company culture is very important and must match or be consistent
    with the corporate culture of the partners.
    "Once you've selected a partner, consider the partner as part of
    your overall strategy.
    Zheng Zichuan suggested that in the selection of partners, we should take the initiative and be early, think about the terms and time plans of the cooperation we hope to cooperate in advance, and communicate with
    potential partners as soon as possible.

    "Tailor-made" overseas solutions for pharmaceuticals

    "Tailor-made" overseas solutions for pharmaceuticals

    After understanding the regulations and selecting the development project, how to lay out and carry out global multi-center clinical trials has become a key consideration
    .
    Similar to the previous article, it is necessary to pay attention to strategy
    in clinical trial development.
    Xu Weijun, Senior Vice President, Head of Greater China and Head of Biotechnology Operation in Asia Pacific of Jingding Pharma, introduced Jingding Pharma's strategic thinking and development experience
    in clinical trials to Pharmaceutical Times.

    Xu Weijun, Senior Vice President, Head of Greater China and Head of Biotechnology Operations for Asia Pacific at Jingding Pharmaceutical

    Weijun Xu, Senior Vice President, Head of Greater China and Head of Biotechnology Operations for Asia Pacific at Jingding Pharma, has over 18 years of leadership experience and management experience in operations including multi-therapeutics, global Phase I III drug/biotrials, and early clinical development and operation strategies
    .

    Xu Weijun

    Xu Weijun said that the phase I clinical trial design is the key, either choose to carry out in China, or because of the characteristics of the product in the United States, Australia or other overseas countries, there are some different clinical trial designs, using the simultaneous development of
    China, the United States and Australia.
    When Phase I is over, international Phase II clinical trials will expand to a variety of regions, including the United States, China, Asia Pacific or Europe
    .
    In the phase III clinical trial, the project will continue to select or expand the country and region of Phase II, and Jingding Pharma hopes to finally help pharmaceutical companies to submit NDAs
    in multiple countries at the same time.
    There are many challenges that will be encountered in this process, and at the same time, these challenges will be manifested in extremely diverse, changeable and complex forms according to the characteristics of the product, the stage of clinical trial, and the different clinical trial areas
    .

    Multiple countries submit NDAs at the
    same time.

    Overcoming these diverse, changeable and complex challenges requires an equally diverse, adaptable, and flexible executive team that maintains close communication with regulators, clinical centers, suppliers, support organizations, and subjects everywhere to solve problems, reduce costs, and leverage the strengths and characteristics of products in clinical trials
    in the shortest possible time 。 Xu Weijun said that considering different environments and different treatment policies, it is very critical when formulating clinical trial plans, and it is necessary to communicate strategically with regulatory agencies such as CDE, FDA, EMA and so on, to reflect the characteristics of the product, in addition to taking into account the allocation of patients, the difference of drugs for different races, etc.
    , to find the current in the specific treatment field, the domestic and the United States, Europe is not the same part
    .

    Overcoming these diverse, varied, and complex challenges requires an equally diverse, adaptable, and flexible executive team

    Xu Weijun introduced a real case that Jingding Pharmaceutical has faced to the pharmaceutical era, and specifically elaborated on the challenges that will be faced in carrying out international multi-center clinical trials, as well as the methods and strategies
    of Jingding Pharmaceutical to help overseas pharmaceutical companies cope with the challenges.
    This case comes from a biotech company with a strong willingness to go to sea, but no experience in clinical trials outside China, which is developing products that are suitable for lung cancer and face fierce competition
    for trial resources.
    Jingding Pharma is responsible for assisting it in completing the global Phase III clinical trial, with the core goal of bringing the product to market as quickly as possible
    .
    In order to formulate the clinical trial plan that best meets the product and select the most suitable test base, Jingding Pharmaceutical has conducted repeated discussions with regulatory agencies in various countries, which can make the test results more acceptable, but it also leads to multiple modifications of the test plan and the need to significantly increase the sample size
    .
    Challenges have emerged in conducting global clinical trials, with the COVID-19 outbreak worldwide, triggering supply chain crises, difficulty enrolling patients, loss of follow-up, and lack of control drugs
    .

    A significant increase in sample size is required

    At the same time, another therapy for the same indication was approved, further exacerbating the difficulty
    of recruitment.
    In order to meet these challenges, Jingding Pharma has provided targeted solutions
    .
    With Jingding Pharmaceutical as the local sponsor to apply for clinical trials outside China, find local suppliers, and better cooperate with local hospitals to solve the difficulties
    faced by subjects.
    According to the changes in the epidemic situation, dynamically select the countries and test bases that can carry out the test, and provide the required support
    according to the requirements of each test base.
    Thanks to the large number of talents and resources in Jingding Pharma in various places, although the sample size was increased during the research process, the completion time of patient enrollment was only 2 months
    longer than originally planned when the epidemic was at its peak.

    Only 2 months longer than originally planned

    Such good results are inseparable
    from Jingding Pharma's resources around the world, thousands of technical and regulatory experts around the world, and strong execution in every link.
    It is worth mentioning that in addition to continuously accumulating and giving full play to resources and experience, Jingding Pharma also has the courage to innovate in clinical trials, thereby increasing the possibility of
    drug approval and marketing 。 Patient-centered trials, taking into account the real clinical needs of patients and many particularities brought about by the epidemic, reduce the rate of patient shedding through remote enrollment, decentralization and other means; Real-world data trials to help pharmaceutical companies develop drugs faster and at a lower cost; In addition, there are innovations in clinical trials such as adaptive design and precision medicine trials, which have optimized the traditional path to market to a certain extent and are increasingly recognized by regulatory agencies
    .

    epilogue

    epilogue

    Although innovative drugs are blocked and long out of the sea, the line is coming, and those who do not quit will be able to look forward to the
    future.
    On the way to the sea of new drugs, in addition to constantly groping for learning and tempering a capable team, it is also necessary to use the help
    of external forces.

    As one of the world's largest clinical CROs, Jingding Pharma participates in 99% of the world's best-selling top 200 drugs, and in 2020 alone, it has supported 1600 clinical projects from 13 therapeutic areas and 110 indications, with rich drug development experience and global resources
    .
    At the same time, Jingding Pharmaceutical has been deeply involved in China for 23 years, with more than 2,000 employees in Greater China, and with its rich local and international business experience, it can spare no effort to help Chinese pharmaceutical companies go global
    .
    When China's innovative drugs meet the international CRO that constantly pursues innovation, the road to the sea of Chinese pharmaceutical companies can be expected in the future, and the Jianchuan Lijian ship tailored for it will sail far and wide sail in the wind and waves more confidently and reach the other shore
    .
    This is also just like the name of Jingding - precise design, full help
    .

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