Topics The 133rd Assembly of the Drug Evaluation Committee held
The 133rd Assembly of Drug Evaluation Committee" was held on November 25, 2019 at Tokyo Shoken Kaikan Hall (Chuo-ku, Tokyo). Under the theme of "'New Modalities in Pharmaceuticals' - Toward the Creation of an Ecosystem for Healthcare Innovation", there were five lectures by speakers from The Office of Pharmaceutical Industry Research, pharmaceutical companies, academia and the Pharmaceuticals and Medical Devices Agency (PMDA). More than 200 people attended the event, and each lecture was followed by a question-and-answer session that lasted until the end of the hour, with cutting-edge topics attracting the audience's interest. A lively panel discussion followed, with the participation of representatives from the Drug Evaluation Committee.
Background
In the past, drug development in the corporate world was dominated by the process of finding hit compounds by screening a small molecule compound library against a target molecule discovered through exploration, and then conducting clinical trials to verify efficacy and safety after passing preclinical trials. In recent years, however, technological innovations in various fields such as cell engineering and genetic engineering have opened the way for the manufacture of biomolecules, cell therapy and gene therapy, which were previously thought to be difficult, and the options for modalities that companies can use in drug development are expanding. In academia, advances in medical science have led to the elucidation of biological processes involved in disease mechanisms, and different target molecule species or biological reactions have emerged as new targets for disease treatment. Medical innovation" is a trend to provide new treatment methods for diseases that were previously thought to be difficult to treat by utilizing the knowledge of academia gained in the field of medical treatment and approaching the causes of disease development with new modalities.
Reflecting recent medical innovations, the Drug Evaluation Committee Assembly Symposium will focus on new medical modalities that can replace small molecule compounds and provide a forum for discussing the differences between old and new modalities, from drug discovery to clinical development.
Symposium
(1) "Research and Development Trends of Novel Drug Discovery Modalities
The Office of Pharmaceutical Industry Research Hideyuki Kagii, Senior Researcher
In recent years, new drug discovery modalities such as nucleic acid medicine, gene therapy, and cell therapy have emerged, showing therapeutic effects on diseases that could not be approached with conventional small molecule drugs or antibody drugs. In light of this, information on the R&D and sales status of each drug discovery modality was analyzed from various perspectives, including development companies, development countries, and types of companies that created the drugs, and the results of this analysis were presented. Interesting results of the analysis were shared, such as the fact that Japan has a high rate of small molecule drugs in development, but low rates of antibody drugs and cell therapy, with China showing a particularly high rate of cell therapy.
(2) "New Developments in Antibody Therapeutics (Bispecific Antibodies)
Tsuyohisa Kitazawa, Director, Drug Discovery and Pharmacology Research Department, Chugai Pharmaceuticals
A presentation was given on emicizumab, which was approved in 2018 and is indicated for the prevention of bleeding tendency in patients with congenital blood coagulation factor VIII deficiency (hemophilia A). He introduced a case study based on his own experience, describing how he developed a bispecific antibody that recognizes two different antigens beyond the framework of conventional antibody drugs to meet the unmet medical needs of hemophilia A, the difficulties he encountered in the process, and how he overcame them.
(3) "Development of CAR-T cell therapy, learning from regulatory filings
Satoshi Kawane, Director, Head of Drug Development Division, Novartis Pharma
He spoke about Kymriah, the first CAR-T cell therapy approved in Japan. He shared how Japan participated in an international clinical development program and how the application was submitted and approved in the U.S., Europe, and Japan using the same data package. Explanation of the special nature of the product, i.e., the importance of establishing a supply chain and thorough quality control in which cells collected from patients are transported to the U.S. manufacturing facility, modified and grown into CAR-T cells, and commercialized, was also given in detail, based on his own experience.
(4) Development of Exon-Skipping Therapeutics
Dr. Shinichi Takeda, Director, National Center of Neurology and Psychiatry, National Institute of Neurology and Psychiatry
He introduced the development process of the exon-skipping therapeutic agent for Duchenne muscular dystrophy (DMD), which he has worked on for many years. He shared his very valuable experience in the development of this drug, starting with the discovery of the exon-skipping therapy through research on the pathomechanism of dystrophin deficiency, followed by the verification of its efficacy in animals (dogs) and its application in the clinic. In October 2015, the MHLW designated the agent as a drug for the Pioneer Review Designation System, and in October 2016, the U.S. Food and Drug Administration (FDA) granted fast-track and orphan drug status to the agent. In addition, it is a successful example of drug discovery originating from academia that has been developed quickly in Japan and the U.S. in collaboration with companies.
(5) "New Modalities and PMDA's Efforts
Dr. Yasuhiro Fujiwara, President, Pharmaceuticals and Medical Devices Agency
He reviewed the efforts from the establishment of the PMDA to the present day, including the level of science and drug discovery capabilities in Japan, and introduced how the PMDA has also focused on the development of new modalities through pharmaceutical affairs strategic consultation. The company has now grown into a review organization that is on par with regulatory authorities in Europe and the U.S., maintaining the world's top level in the duration of new drug review and realizing highly predictable reviews. Based on the experience of the four trial implementations of the Pioneer Review Designation System, the lecture also gave rise to expectations for further activities by the PMDA.
Panel Discussion
There was discussion on how the decision to move from non-clinical to clinical development with new modalities is made. While it is an important requirement that the efficacy be confirmed in nonclinical studies and that the quality of the drug be ensured, there was also discussion about the need for careful judgment as to whether the existing clinical evaluation methods can be used with the new modality, and the difficulty in making such judgments. In addition, there was a request for flexibility in PMDA consultation when developing new modalities, as well as the need to proceed with development while working together to create new guidelines, and expectations were expressed for future collaboration between industry, academia, and government in new modalities.
Panel discussion
Concluding Remarks
At this Drug Evaluation Committee Assembly Symposium, we were able to share with many participants the latest status and experiences of efforts being made by academia, regulatory authorities, and pharmaceutical companies on "new modalities for drugs," and had fruitful discussions during the Q&A session and panel discussion. Many participants as well as speakers commented that the symposium was well received.
We hope that this symposium will be useful in your future efforts to develop new modalities, and we would like to thank all the speakers and other members of the planning committee for their cooperation in making the symposium a fulfilling one.
( Chikara Kikuchi, Vice Chairperson, Drug Evaluation Committee)