The thrill of working on clinical pharmacology for new drug candidates

Naoki Kotani majored in pharmacokinetics at university and hoped to find a clinical pharmacology position with a pharmaceutical company. He was particularly drawn to Chugai Pharmaceutical due to its abundance of development pipelines that had the potential to deliver more and better medicines to patients. Believing that this would give him many more opportunities for him to contribute to the development of medicine, he decided to join the company. He has been consistently engaged in clinical pharmacology throughout his 10-year career with the company. The role of the person in charge of clinical pharmacology includes working as a member of pharmaceuticals development project teams, evaluating the pharmacokinetics of new drug candidates and how it relates to efficacy and safety, and the design of dosage and administration of the candidate drug to different patient groups for clinical trials. ‘The appropriate design of the clinical trial connects to the success of the development. It is by no means an easy task, but it is an extremely important role and I find it very rewarding.’

Kotani has been involved in various drug development projects. One that left a particularly great impression was the development of a novel antibody drug for hemophilia A. ‘Hemophilia A is a disease that causes blood-clotting disorders. Previous standard treatments have required the repeated, extremely frequent administration of highly invasive drugs, which I had heard placed a great burden on patients and their families in terms of living their daily lives. Under these circumstances, our novel antibody drug was expected to achieve treatment efficacy with a less burdensome method of use. In an early-stage clinical study for this drug, in which I was involved in the clinical pharmacology role, the prophylactic effect on bleeding in patients was confirmed as clinical data. When I heard that delighted feedback had been received from the patients who took part in the clinical study as subjects, it gave me a real sense that I could help patients through drug development. The thrill I felt at that moment still remains strongly in my heart and serves as my motivation to this day.’ That antibody drug has now grown to become one of Chugai Pharmaceutical’s core products.

Absorbing cutting-edge knowledge and insights into M&S during posting to the United States

*M&S: Short for Modelling and Simulation

In his seventh year with the company, Kotani was given a major opportunity. He was posted to Genentech, a Roche Group company based on the west coast of the United States. ‘Building my career overseas has been one of my aspirations since joining the company. In my career development interview, I emphasized the fact that I wanted to improve myself by absorbing the knowledge and insights of the Roche Group, which is engaged in cutting-edge drug development on a global scale, and I was given an opportunity to work in the United States. My mission was to absorb the modelling and simulation (M&S) techniques and expertise that Genentech is implementing.’ M&S refers to modelling, that is using accumulated clinical data to build mathematical models that express the pharmacokinetics of new drug candidates and how it relates to efficacy and safety, and using those models to simulate the outcomes of clinical studies. This is a hot, cutting-edge theme in the pharmaceutical industry today.

In his two and half years in the United States, Kotani gained truly valuable experience. ‘At Genentech, I participated in development projects for an asthma drug and a cancer drug using M&S. I worked very hard to analyze clinical data with nonlinear mixed-effect models and to conduct simulations to support the design of dosage and administration of the candidate drug. I was really surprised by the fact that, in the Unites States, government authorities actively took a leading role in establishing the environment to promote drug development with M&S. At Genentech, I saw numerous cases that, depending on the conditions, showed potential for M&S-based studies to become an alternative to conducting new clinical trials. It would be possible to complete a clinical study in the digital realm, without the need to gather patients and other subjects to conduct a new clinical trial. If we can skip clinical trials, which cost enormous amounts of money, this would cut down on development costs and approvals could be obtained much more quickly. The efficiency of drug development would improve drastically, which would also bring major benefits to patients. Every day, I poured myself into the work of development, excited by the thought of how far the world had progressed.’

A desire to lead Chugai Pharmaceutical’s future with M&S

Having returned to Japan with world-class M&S knowledge obtained at Genentech under his belt, Kotani is now working on deploying M&S in ongoing clinical drug development projects. He also hopes to implement M&S in translational research, which is a bridge between preliminary non-clinical research and clinical development. ‘If we can build a platform that directly connects non-clinical data obtained through animal experiments to human clinical predictions, drug development will become more efficient. I am working on devising this kind of new M&S strategy, discussing it with other members of the Research Division as I go.’

In the near future, it will become possible to conduct analysis with M&S to a level that shows how drug-candidate compounds react in the human body. Kotani is enthusiastic about playing a leading role in making that kind of world a reality. Achieving this will require knowledge of biology and clinical medicine, and Kotani will need to upgrade his own knowledge and experience. It will certainly not be easy, but he is still inspired by his experience in the development of the antibody drug for hemophilia. A drug that he helped to develop freeing patients from suffering and changing their lives. Kotani wants to deliver that feeling of joy to as many people as possible. It is with that passionate commitment in his heart that Kotani continues to address difficult challenges today.

*The contents of this article, and the divisions that the people featured in this article belonged to and the names of those divisions are current as of the time of the interview.