Alzheimer's disease is a chronic, progressive neurodegenerative disease that affects the memory, thinking, and behavior of millions of people worldwide. Currently, researchers around the world are working to find innovative** ways to meet the needs of patients and families. In June last year (2023), the U.S. Food and Drug Administration (FDA) announced that it had fully approved the marketing of Leqembi (generic name: lecanemab), a new drug for Alzheimer's disease (AD). It is also the first new Alzheimer's drug to receive full FDA approval in 20 years. Leqembi was jointly developed by Eisai and Biogen. It can be said that lacanemab, as a successful case of Alzheimer's disease drug development, fully reflects the importance and advantages of IPD integrated product development.
Company Presentation
Eisai is a global company headquartered in Tokyo and founded in 1941 as a global company specializing in the research and development of pharmaceutical products. It is a pharmaceutical company that conducts R&D, production, distribution and marketing business worldwide, and its products are mainly innovative drugs in the fields of neurology and oncology. Its overseas branches, subsidiaries and factories are located in Europe, America, Asia and other parts of the world. As of the end of fiscal 2019, Eisai had 10,998 employees worldwide. Over the past 70 years, Eisai has grown from a small lab with 15 employees to one of the top 20 global companies in the pharmaceutical industry. In 1955, Eisai developed the popular "Chocola" vitamin line, and at the same time changed the name of "nihon eisai" to "eisai".
From 1976 to 1986, Eisai began to invest globally and was committed to building world-class infrastructure. On the other hand,Eisai strengthens its leadership in R&D in the field of vitamins and develops a best-selling drug, Juvela. In May 2016, the FDA approved lenvatinib in combination with everolimus** in patients with advanced renal cell carcinoma (RCC) who had previously received anti-VEGF. In February 2015, the FDA approved it for differentiated thyroid cancer. Phase III clinical trials for liver cancer are underway. In January 2016, the FDA approved eribulin for patients with advanced or metastatic liposarcoma who had previously received an anthracycline-containing regimen**, which had previously been approved for metastatic breast cancer.
Implementation of IPD background
In the 60s and 70s, benefiting from the expansion of medical insurance, Japan's pharmaceutical industry entered an accelerated growth stage of exponential growth, and many pharmaceutical giants began to emerge at this time. After entering the 80s, Japan entered a stage of medical insurance cost control similar to the current Chinese pharmaceutical industry, and drugs were strictly controlledThe growth rate of the pharmaceutical industry declined, during which the company's stock price basically grew at zero in 10 years due to the cold winter of the domestic pharmaceutical industry and the increase in the company's R&D investment. Even in the 90s, there were several years of zero growth, or even negative growth.
Eisai's core business is prescription drugs, but in order to continue its sales scale, Eisai also operates OTC, nutraceuticals, and generics in Japan. However, due to Japan's frequent control of drug prices, the profits of generic drugs are very low, international generic drug companies have withdrawn and fled, and the profitability of local generic drug companies is generally not as good as that of international generic drug giants such as Teva and Sandoz. Because Japan's ** frequently controls drug prices, the profitability of generic drug companies has declined significantly.
As a result, Eisai has clarified the development idea of taking innovation as the strategic orientation and the new overseas strategic focus. Quickly develop the focus of the company's production and operation from OTC and generic drug products with low innovation value, fierce homogeneous competition, and strict control to innovative drugs with high clinical value, high degree of scientific research and technological innovation, large market space at home and abroad, and certain cost control immunity. Thanks to the IPD product development system, Leqembi is the second Alzheimer's disease** drug approved by the FDA after aducanumabIn June 2021, Biogen's Alzheimer's disease drug Aduhelm (aducanumab) was approved for marketing, which is the first drug of its kind to be fully approved by the FDA since 2003. The full FDA approval marks a milestone for Alzheimer's disease**. Eisai has maintained rapid growth since the 90s, and its market value has exceeded 10 times since 92.
Analysis of Eisai IPD system in Japan
In recent years, with the development of science and technology, the field of pharmaceuticals has also made great progress. Generic drugs, biosimilars, innovative drugs, etc., are dazzling, and the continuous enrichment of drugs provides an effective guarantee for human life, health and safety. With the strong support of the first country, more and more drugs have been included in the medical insurance system. However, if we have always relied on imports and imitations, we can only follow others and cannot achieve transcendence. If Chinese pharmaceutical companies want to achieve corner overtaking, they must make efforts in innovative drugs. It is not difficult to find that many pharmaceutical companies invest a lot of time, manpower, and financial resources in the research and development of innovative drugs every year. The implementation of the IPD system within the enterprise is an important secret to achieve how fast and cost-effective product development is. Due to the competition with domestic companies or the world's leading enterprises, the development experience of Japanese companies may have reference significance for domestic enterprises. Therefore, this time, we will focus on the successful development case of lacanemab as an Alzheimer's drug, and learn how Eisai implements the IPD system within itand became one of the top five pharmaceutical companies in Japan.
Product portfolio management responds quickly to customer needs
A good plan is half the battle, especially for a business that pursues business success, every investment must strive for a good return, which determines the importance of demand management. At the same time, in the face of the ever-changing market environment in the process of product development, good demand change management is a necessary condition for successful product development. Alzheimer's disease is a progressive degenerative disease of the nervous system with insidious onset. It is mainly manifested by cognitive decline, psychiatric symptoms and behavioral disorders, and a gradual decline in the ability to perform daily living. Currently, there are more than 50 million people with dementia worldwide, of which about 60-80% are AD. In China, the number of AD patients is expected to increase from 10 million in 2020 to more than 40 million in 2050, and the incidence of AD is increasing as the population ages rapidly. There is a growing need for innovation** from Alzheimer's patients and medical professionals, and the unmet need is enormous.
Not only does Alzheimer's disease cause great disaster for patients and their families, but it also has a large number of negative social effects, such as decreased productivity, increased social costs, and disease-related anxiety. Alzheimer's disease has a positive impact not only on the individual but also on society as a whole. Product demand plays a decisive role in the goal and scope of product development projects, and sufficient demand analysis is the basis for the success of product development. Under the IPD system, the routine activities of product portfolio management are first and foremost manifested in the rapid response to customer needs. This includes end-to-end business flows such as requirements collection, analysis and decision-making, and R&D implementation. Requirements management is essentially a business flow of "from the customer to the customer". The requirements management process is to efficiently coordinate various departments and better manage the whole process of customer needs being met.
Due to the fact that the mechanism of the disease is not fully understood, and the clinical trial review process is very strict, in the past 20 years, the failure rate of new drug development in AD has exceeded 98%, which is the highest failure rate of new drug development in all fields. Over the past decade or so, most Phase III clinical trials have failed. Eisai has been deeply involved in the field of Alzheimer's for many years, and Eisai has been researching Alzheimer's disease for nearly 40 years since it first entered the field of Alzheimer's disease in 1983. And the company has been focusing its business resources on the field of dementiaEisai successfully developed aricept as the standard for Alzheimer's disease in '97**. Not long ago, the innovative drug lacanemab (lecanemab) was approved by the National Medical Products Administration (NMPA) to officially enter China for mild cognitive impairment caused by Alzheimer's disease and mild dementia caused by Alzheimer's disease. As the world's first breakthrough targeted drug for AD**, the approval of LACANEMAB will lead AD** into a new era of "anti-cause**".
Adjust the organizational structure, integrate R&D resources, and focus on core business
H3 Biomedicine was founded in 2011 by Eisai with a $200 million investment to develop a precise** approach to cancer by combining the resources and expertise of a large pharmaceutical company with the acumen and innovation of a small biotech company. Its core product in the pipeline, H3B-6545, is a small molecule selective estrogen receptor covalent antagonist for breast cancer patients with estrogen receptor mutations, which has entered phase II clinical trials. In addition, there are several other products for liver cancer, bladder cancer, solid tumors and hematologic tumors. It can be seen that H3 is not a dispensable subsidiary, but an important innovation and new drug development engine with outstanding results, but Eisai announced its closure in 2022.
For Eisai, although it is not the world's top multinational pharmaceutical company, it also has blockbuster products that can change the pattern and a huge global organizational structure. Eisai is one of the few companies that mainly rely on its own research and development, rarely expand its pipeline through large-scale mergers and acquisitions, and its core products are mostly developed in cooperation with other multinational pharmaceutical companies. With the advent of the risk of lenvatinib patent expiration, in this case, Eisai took the most decisive attitude to shake off the burden and adjust its organizational structure. Eisai did not choose to go through the next stage by introducing pipelines and licensing in products, butIntegrate global R&D resources, use emerging technologies, and cultivate internal skills to develop drugs more efficiently.
In 2022, Eisai announced a decision to restructure its global research and development (R&D) organization from the previous business group structure to a new R&D organization with the concept of DHBL (Deep Learning in Human Biology). Eisai has elevated lecanemab, a new Alzheimer's disease drug developed in collaboration with Biogen, to a strategic level. According to Eisai, the R&D, regulatory, medical, value, access, marketing and alliance management functions related to disease modification** (DMT) for Alzheimer's disease and related brain diseases, including lecanemab, the next generation of Alzheimer's disease**, are the most important projects. Eisai also announced that the new organizational structure was also launched on October 1, 2022. Prior to this, the Neurology Group, the Oncology Group, the Drug Development Center, and the HHC Data Creation Center were also disbanded. With resources focused on the research and development of new drugs for Alzheimer's disease, and Eisai's deep accumulation in the field of neurological diseases, Lecanemab has been successfully developed and proven for the first time to alleviate the onset of Alzheimer's disease, breaking the deadlock of new drugs for Alzheimer's disease.
A clear strategic vision and a clear direction for success
Product strategy starts with a clear strategic vision, which is a vision with clear direction and content. The core strategic vision gives a picture of the company's long-term goals, how the company expects to achieve them, and why the company is likely to succeed, and guides the various elements of a product strategy. Eisai is one of the first Japanese leading pharmaceutical companies to focus on overseas marketsEisai began in 1941 and began its comprehensive overseas expansion in the late 60s of the 20th century, and in 1992 established laboratories in Japan, the United States and the United Kingdom, which is Eisai's three-center R&D network. Among them, the Tsukuba Laboratory in Japan began research on the discovery of dementia drugs in 1983, and established an R&D team to develop anti-cancer drugs in 1987.
Based on the vision and mission of the strategy, we must pay attention to the two major strategies related to products, one is the product line strategy and the other is the product platform strategy. The product line strategy belongs to the experience development strategy of the product line, which is specifically realized by the roadmap planning of the product line, and finally the product development is carried out according to the product roadmap planning. Eisai began its globalization process in the 90s with a three-step long-term plan. Eisai has established a full-process system covering R&D from R&D to final production and marketing, and has established R&D institutions in the United States and Europe, forming a three-center R&D network spanning Japan, the United States and Europe. After that, although Eisai launched new products, due to the dispersion of R&D resources, Eisai faced the situation of not being able to launch new products after a series of **, and subsequentlyEisai has pooled its resources in neurology and oncology and launched a series of products in collaboration with partners in neurology and oncology.
In addition, based on the aging of the Chinese population. In 2020, Eisai China partnered with Alibaba Health and Chinese internet giant JD.com to build an online platform focusing on medical and health services for the elderly, achieving full coverage of the entire medical process, health scenarios, and user life cycle for the elderly. Eisai leverages its advantages in the field of neurological technology and fully integrates with JD Health's advantageous businesses such as pharmaceutical e-commerce and Internet medical care to provide the elderly with simplified medical treatment procedures and online and offline disease education. Later, this platform was named "Silver Hair Pass". In 2021,"Yinfa Tong" obtained the Internet hospital license issued by the Shanghai Jing'an District Health Commission. In Shanghai, Eisai China is also the first company to be approved as an Internet hospital.
Multi-department team coordination to improve R&D efficiency
Most innovative pharmaceutical companies need a certain amount of room for growth, and the short-term logic can only incubate fast-follow, but cannot give birth to a real first-in-class. Rather than emphasizing R&D investment, it is more important to improve R&D efficiency. The development of a new drug is a long process from the start of the idea to the launch of the final product, which can take nearly a decade, and it takes hundreds of processes to develop a successful drug. There is no doubt that there is an extremely complex process behind the development of new drugs from R&D to marketingThrough the IPD project team, this complex and lengthy process was reorganized, and the end-to-end new drug development process was divided into eight stages: project discovery, development, clinical phase I, clinical phase II, clinical phase I, registration and marketing, and life cycle. During the development of Lacanemab, the drug development team adheres to the principles of IPD and coordinates multiple departments and teams.
The global confirmatory phase III CLARITY AD trial in patients with early-stage Alzheimer's disease met the primary endpoint and all secondary endpoints: a significant change in the Cognitive Function Scale (CDR-SB) after 6 months compared to the placebo group, and an improvement in clinical decline symptoms at 18 months, with a percentage reduction of 27%. The incidence of amyloid-related radiographic abnormal edema (ARIA-E) was 125%, and the incidence of ARIA-E in the placebo group was 17% (according to other studies, the incidence of ARIA-E in the ADUHELM group was 35% in the ADUHELM group and 27% in the Donanemab group). They have carried out the chemical synthesis of drugs, formulation development, pharmacokinetic studies, and safety evaluation. Phase II effectiveness results showed a decrease in the Alzheimer's Disease Composite Score (ADCOMS) and other measures from baseline at 78 weeks, along with rapid and deep clearance of amyloid plaques.
Project management at lacanemab involves project evaluation, resource allocation, and timing. The drug development team develops a detailed project plan and monitors the progress and key milestones of the project. Currently, Phase III AHEAD 3-45 and Phase II III dian-TU (in combination with anti-taumab E2814 developed by Eisai) prophylaxis studies are being conducted in patients with preclinical Alzheimer's disease and patients with mutations in the genes that cause Alzheimer's disease, respectively. They communicate and report regularly with senior management to ensure the smooth progress of the project and the achievement of goals. Through cross-departmental collaboration and information sharing, they optimize the chemical structure, drug release characteristics, and bioavailability of drugs to ensure drug quality and efficacy. Supported by the positive results of the phase III study, lecanemab (and other putative DMTs) should easily become a best-selling product based on a combination of population size, market demand, and pricing.
Project pipeline management ensures that projects are completed on time and with quality
Project management is the key to bringing cross-functional teams together to act better. You need a goal first, then turn the customer needs into product needs, and then develop a detailed plan. Next, the activities are scheduled, and each activity is budgeted and resources are allocated, which can be dynamically allocated during the implementation of the project, but the commitment of the PDT cannot be changed. Pipeline management is similar to resource scheduling and processing in a multitasking system, which refers to the process of prioritizing and dynamically balancing development and the resources it needs according to a company's business strategy. Eisai's core business is prescription drugs, but in order to continue its sales scale, Eisai also operates OTC, nutraceuticals, and generics in Japan. At present, the company has a number of products on the global market, including the anti-cancer drugs hal**en (eribulin mesylate) and lenvima (lenvatinib), the anti-epileptic drug fycompa (perampanel) and the anti-insomnia drug dayvigo (lemborexant).
Project management should be integrated into the concept of the whole life cycle, from concept formation to plan execution, to development, verification, and product release, to form project pipeline management, and to invest resources in stages. At the beginning of the project, an in-depth survey was conducted, a large amount of data was collected through IPD methods and tools, and a comprehensive analysis of the competitive situation was conducted. As a result, a clear product positioning can be generated, which can supervise the project team for the urgency and execution of new drug development. During the project planning phase, develop alternatives for high-risk points. In the process of new drug development and execution, the management of plan changes is strengthened, the control process and form are specified, and the control is carried out through the milestone monitoring and early warning system. to prevent schedule delays and ensure that new drug development progresses as planned.
Risk management is required at all stages of new drug development. Analyze the causes of risks and the extent of hazards, and formulate countermeasures based on the probability of occurrence. Continuously detect risks and control the damage caused by the occurrence of risks to mitigate the impact of risks on the project. For example, project management plays a key role in the development of lacanemab. Project managers work closely with team members to ensure that projects are completed on time and with quality. They develop detailed project plans and milestones and track the progress of team members' work. Through effective communication and problem solving, the project manager coordinates the cooperation of various teams to ensure that the project is completed within the scheduled time and budget.
Full life cycle management to achieve sustainable development
Better understand customer needs and competitive dynamics before new drug development, define and develop differentiated products with competitive advantages, and realize the commercial value of products and continuous product improvement through product life cycle management. Product life cycle management was proposed by Professor Jiang Xin'an, the founder of Yisi Consulting, and is widely recognized by the industry as the father of product life cycle WPLM. He summarized the whole life cycle of products into seven parts: product strategy, product market, product demand, product planning, product development, product launch, and product market life cycle management (or life cycle). Product life cycle management is to determine the development goals and strategies of product lines through market management, and of course, company-level product strategy is an important input of market management.
Based on the results of market management analysis, product planning is formulated, and customer needs, external drivers and internal needs are analyzed. Determine the product development task book, establish the project to develop the product, prepare for the market in all links, make full use of the 4P tool to do a good job in marketing strategy, train sales personnel, introduce products into the market, and terminate product sales, reposition the product strategy according to the keen insight of product management personnel, and enter the next cycle, so that the product is sustainable and the enterprise can achieve sustainable development. In addition, the product life cycle is also a powerful tool used by product personnel to describe the product and how the market works, and it is also a product development roadmap for R&D personnel to develop products.
Therefore, the successful development of lacanemab relies not only on scientific and clinical data, but also on an effective marketing strategy. The drug development team worked closely with the marketing team to develop a marketing plan for physicians, patients, and health insurance providers. They communicate the clinical value and efficacy benefits of lacanemab to the medical community by holding academic conferences, participating in industry exhibitions, and publishing scientific articles. In addition, the development of lacanemab does not mean the end of the task, but the beginning of the life cycle of a new drug. The drug development team continues to collaborate with regulatory agencies and medical experts for follow-up monitoring and research. themCollect safety and efficacy data during drug use, and continuously optimize drug usage guidelines and dose adjustments. Through lifecycle management, they ensure that lacanemab continues to meet the needs of patients and the healthcare community at different stages.
Finally, through the IPD system, Eisai successfully promoted the development of lacanemab and realized its clinical value, which provides a useful reference for future drug development. In addition, with the help of the IPD system, Eisai has realized a health management platform for the whole life cycle health management scenario, providing medical services driven by digital technology based on an effective chain. China's pharmaceutical companies are based on the background of medical insurance reform, volume procurement, two-invoice system and other policies, as well as the economic downturn squeezing the overall revenue and profit growth space of the industryPromoting the transformation of the development of the pharmaceutical industry to innovation-driven through the IPD system is an important means to improve the stability and competitiveness of the industrial chain.