The Pharmaceutical Manufacturers Association of Japan (PMAJ) held a media forum. Diverse Values of Pharmaceuticals "What are the diverse values brought by new modalities - Spinal Muscular Atrophy (SMA) as a case study
On March 7, 2025, the Pharmaceutical Cooperative Media Forum was held at Muromachi Mitsui Hall & Conference (Chuo-ku, Tokyo). This year's theme was "What is the diverse value brought by new modalities - a case study of SMA (Spinal Muscular Atrophy)," with lectures by Yuko Oyama of the SMA Family Association, Reiko Arakawa of the National Center for Global Health and Medicine Hospital, and Tsugoru Goto of Keio University, and a three-person panel discussion facilitated by Kazuhiko Mori, Executive Director of the Pharmaceutical Manufacturers Association of Japan (PAK). A panel discussion was facilitated by Mr. Kazuhiko Mori, Executive Director of the Pharmaceutical Manufacturers Association of Japan (PMAJ). More than 120 people, including media and member companies, attended the event at the venue and via webcast.
Forum
Background of the Forum
In recent years, drugs utilizing new drug discovery modalities, such as nucleic acid drugs and gene therapy drugs, have emerged and are having a significant impact on the treatment of areas such as cancer and genetic diseases, which have been difficult to treat in the past. In this forum, we asked three opinion leaders to speak about SMA, the challenges posed by the disease, and examples of the diverse value of pharmaceuticals in addressing these challenges. The following is a transcript of their presentations.
Opening Remarks
Kazuhiko Mori, Executive Director, Pharmaceutical Manufacturers Association of Japan
In order to create such innovations, "evaluation" is important, and it is necessary to evaluate and discern drugs from various perspectives. It is precisely because of these evaluations that better products can be created next time. In particular, evaluations from patients are the most important and motivating factor for pharmaceutical companies.
Scientific evaluation must be objective and quantitative, but in some cases it is difficult to measure. In addition, evaluations differ from stakeholder to stakeholder, so how to integrate them is also an important issue.
Figure 1: Diversification of modalities
In 2025, the Pharmaceutical Manufacturers Association of Japan (PMAJ) released "Industry Vision 2035." This vision consists of three pillars, and the first pillar, innovation, includes working together with patients. In the future, we believe it is more important than ever before for patients and various stakeholders to work together to lead to new drug discovery innovations ( Figure 2).
Figure 2.Pharmaceutical Cooperative Industry Vision 2035
Subject 1: SMA Practice Changed by Therapeutic Drugs
Dr. Reiko Arakawa, Medical Director, Department of Clinical Genomics, National Center for Global Health and Medicine
SMA, a genetic disease with a fatal course in infancy
SMA is a disease in which loss of SMN1 gene function causes loss of anterior horn cells in the spinal cord and muscle atrophy ( Figure 3). It is characterized by extreme weakness of the trunk muscles and muscles close to the body, especially around the neck, shoulders, and hips. As a result, in severe cases, the child will not be able to sit up or crawl. The incidence of SMA is 1 per 20,000 live births, making it the most frequent single genetic disease with a fatal course in infancy and progressive neurodegeneration in untreated cases. Patients with type I have decreased respiratory function during infancy, resulting in respiratory failure. As a result, it is difficult for them to survive beyond the age of 2 years without the use of an artificial respirator.
Figure 3. What is SMA?
Life-Changing Treatment Beyond Effectiveness
The history of this disease was reported in a paper in 1980, and the gene was identified in 1995. Subsequently, genetic testing was introduced in Japan in 1996, and the concept of the disease was established. With the disease concept clarified, the SMA Family Association was established in 1999 ( Fig. 4).
Figure 4: From gene identification to establishment of disease concept, development of therapeutic drugs, and formation of family associations
In the double-blind comparative study in which I participated, the actual drug and the sham drug were tested indistinguishably. One child's breathing became progressively worse and required a ventilator, while the other child was able to raise his hands and play without the use of a ventilator. I was shocked not only by the effectiveness of the treatment, but also by the fact that there were almost no side effects, that the drug improved muscle strength in children with weak muscles, and that the therapeutic drug changed the lives of these children.
Currently, there are three types of therapeutic agents for SMA: gene therapies, nucleic acid drugs, and small molecule drugs. Each of these therapies has unique characteristics and plays a major role in the treatment of SMA.
Newborn Screening - Aiming for Earlier Treatment
Newborn screening has revealed the usefulness of early treatment of SMA. Even if treatment is started after the patient is on a respirator, it is difficult to remove the respirator afterwards, especially in SMA Type I, where neurodegeneration progresses rapidly and motor function is severely impaired. According to data from the U.S., if treatment can be provided within the first 14 days of life, most children will gain ambulation, and the lives of these children will be changed dramatically. This requires medical and social efforts. Against this background, public funding of newborn screening is being promoted through the efforts of family associations.
In addition, in the United States, newborn screening will be developed as a national system starting in 2024. The effect of early treatment through newborn screening is clear: 76% of severely ill patients with SMN2 of 2 copies can attain ambulation if treated before the onset of disease. After onset, only 19% do. This has a significant impact on the patient's lifetime (see(Figure 5).
Figure 5: Effects of early treatment through newborn screening
Meanwhile, in Japan, the Administration for Children and Families has launched a demonstration project for newborn mass screening. Although expanded newborn screening covers almost all prefectures, not all children are eligible for it, and in some areas it is conducted at their own expense. As a result, there are still many children who are overlooked and develop the disease. As a public health program, it is hoped that it will be implemented equally throughout Japan ( Fig. 6).
Figure 6: Expanded Screening Implementation in Japan
Ongoing Challenges
If treatment can be started within 14 days of birth, the lives of these children will change dramatically, but it is difficult to conduct tests, diagnosis, and treatment explanations within this time frame, and the limited number of medical institutions that can handle this is a major challenge.
In addition, medical care is not necessarily unnecessary after treatment. Children treated for Type I may develop scoliosis and dislocation as they try their best to sit up with their weak bodies. In the U.S., surgery is performed to insert screws, but since stainless steel screws are not distributed in Japan, dislocation often occurs even with the most expensive treatment. In addition, support for the family is also necessary. It is a great shock when your child is diagnosed with SMA after you thought he or she was born in good health. It is also very important to provide a good genetic counseling system to ensure that parents are informed and accept the fact that there is a cure and that a diagnosis has been made ( Fig. 7).
Figure 7. Team medical care in SMA
Integration with cybernics therapy is a new challenge to improve motor function and walking. Combining devices such as robotic suits with drugs can reduce the burden of caregiving and help patients become more independent. Therefore, there is a need to develop small devices suitable for children. In addition, the scope of treatment has expanded with the inclusion of SMA in newborn screening and the spread of genome analysis. It is important to seek appropriate treatment methods in dialogue with society, including the proper use of expensive therapeutic agents.
Title 2: Hope of New Modality - Perspectives of SMA Patients' Families
Yuko Oyama, Chairman, Spinal Muscular Atrophy Association of Japan
SMA and therapeutic agents
The earlier the onset of SMA, the more severe the disease; in Type I, which develops by 6 months of age, 90% of patients will die by 2 years of age without respiratory management.SMA has long been considered incurable, but since 2017, three innovative treatments have been introduced ( Figure 8), making it a curable and even preventable disease SMA is now a curable and preventable disease.
Dramatic improvement in symptoms
In the absence of curative drugs, children with SMA required respiratory support within weeks of birth and were bedridden, unable to sit up or stand for the rest of their lives. However, there have been cases of children with severe SMA who needed respiratory support as early as two weeks old and would have died within a few months, but who were taken off the ventilator and practicing walking with a walker at the age of five years after starting treatment at six weeks. This is a phenomenon that would never have been possible with SMA in the past, and such a significant change has brought very great hope to families with children with SMA.
Figure 8. Medications for SMA
Below are some examples of patients and their families introduced in the lecture.
Positive energy and motivation to never give up
We have received messages from parents of SMA siblings. The older brother received a definitive diagnosis at 10 months of age and began treatment at 11 months. On the other hand, the younger brother received a prenatal diagnosis and started treatment at 5 days of age.
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Messages from Fathers
Through gene therapy, my second son, who could not even turn over, is now able to sit up and pedal a wheelchair. He is doing his best in rehabilitation and spending happy days with his friends at the children's preschool and the rehabilitation center. He loves cars and is excited about his future dreams. Being able to move his body by himself has given him confidence, and he is now challenging himself to various physical activities, including baseball. My third son has developed in an age-appropriate manner, including in terms of movement, thanks to early treatment. I feel that my healthy days are made possible by the treatment. For my family, I feel that my second and third sons' healthy growth through treatment gives us energy to spend our daily lives in a positive manner.
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Messages from Mothers
We later realized that our second son had a hard time moving his body freely before his treatment. We were shocked when we found out about the disease, but more than that, we were relieved to have a clear diagnosis. It was just the year that gene therapy was approved, and I feel grateful to have been born in an era when treatment was available. In the four years since my treatment, I have been able to do a little more, but I am sure that I will face new challenges in the future, such as scoliosis. However, I feel that both parent and child are motivated to rehabilitate themselves, not giving up on standing on their own feet and walking. My third son is now growing up really naive. As a parent, I am constantly worried and anxious about the fact that my son will have to live with SMA for the rest of his life, but I hope that we can stay positive while experiencing his growth together with those who support us.
No need for medical care New dream "I want to walk!
Not only for infants, but also for patients whose symptoms had progressed some time after the onset of the disease, the advent of pharmaceuticals was of great value. One such example is a junior high school girl who bravely sent us a message this time.
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Messages from Junior High School Students
I started treatment 7 years ago and now, for a short time, I am able to sit alone and lift my legs a little. I am getting better little by little, but there are still many things I would like to do and be able to do. In the future, I would like to be able to walk, jump rope, and do iron bars.
She used to have to wear a ventilator at night, but the treatment has allowed her to spend more time without a ventilator. Also, she used to receive nutrition through a gastrostomy, but now she is able to eat almost everything on her own. And he is now able to have a new dream of walking, and is doing very well in his rehabilitation, including practicing walking using a robotic suit.
Expansion of schooling and work opportunities
This is a high school student who started treatment 10 years after onset of disease. He operates communication devices with switches on his fingertips. Previously, he could only press the switches 10 times per minute, but with treatment, he can now press them up to 33 times. This has enabled him to operate the devices freely, and he has now started working at a café by operating a robot. I operate switches with the fingers of both hands, use two iPads and a computer at the same time, and guide customers via a robot placed in the café. Even though the visible changes are small, these small changes have allowed me to gain opportunities for schooling and employment, which opens up great possibilities for my future.
Slow progression
Therapeutics brings value to the lives of adult patients. Message from a Type II woman. She feels that the treatment has slowed the progression of her symptoms and improved and maintained her function.
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Message from an Adult Woman 1
I am type II and use a ventilator when I sleep and a power wheelchair when I go out; I need assistance from family and helpers 24 hours a day, and at home I draw on my computer while lying in bed. I started the therapeutic medication in January 2022, which is 3 years ago. Before taking the medication, my hand to hold a spoon got tired easily, but two weeks after taking the medication, I can eat out one yogurt. When writing letters, I used to run out of strength after one line, but now I can write about 10 lines, and I was happy when I could write a letter to a friend. There have been no major changes since then, but I feel that the progression of my symptoms has been minimal. Even if there are no major changes in my body, just slowing down the progression of the disease is a big benefit for me. Slowing down the progression means that I have more time to challenge my dreams and goals. I will continue to do my best every day with my medication and the support of those around me.
Thus, here she is in bed with a mouse, working on a computer to illustrate
Promotion of social participation
This is another woman who started treatment decades after the onset of the disease.
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Messages from Adult Women 2
He is Type II and wears a ventilator 24 hours a day. I usually work remotely as a publicist for the SMA Family Association, and I started the SMA meds in the fall of 2021, which makes this my fourth year on them. the first thing that happened after starting the SMA meds was that my stomach started to move and the abdominal pain after eating was gone like a lie. In the area of the mouth, a university teacher who studies the voice commented that my speech was smoother and my voice clarity was better than before. And my finger joints have become softer and less tired, and the best thing about starting SMA treatment medication is that I have more opportunities to eat well with friends, participate in university research, operate a computer smoothly, and participate in social activities. I hope to continue SMA therapeutics in the future.
She is also bedridden, but now that her physical condition has been improved by the treatment, she is participating energetically in society, with a computer at her fingertips. She has become an indispensable worker for our association.
We have received many other appreciative comments about the treatment (seeFigure 9 (Figure 10).
Figure 9. Voices of Patients' Families
Future Challenges
While the value of treatment is thus immeasurable, challenges also exist. The highest priority issues are the establishment of systems such as newborn screening for early diagnosis and treatment, and the uniformity and elimination of regional disparities in SMA treatment throughout the country. Quantitative evaluation in line with actual conditions is also necessary. Currently, physical function is assessed by the World Health Organization (WHO) exercise milestones, but new assessment criteria are required to accurately evaluate the impact of minute changes on patients' lives.
Furthermore, it is necessary to calculate appropriate cost-effectiveness, taking into account costs related to education and welfare other than medical expenses, as well as lifetime income including the patient and his/her family. The evaluation should also include quality of life, such as the decrease in medical care and daily living assistance and increase in productivity that result from the treatment. Further augmentation of effectiveness is also required by patient families, and we look forward to future developments.
Finally
Our association (Figure 10. The MMA was established in 1999 and celebrates its 25th anniversary in 2025. Currently there are about 300 member groups, and members range in age from 0 to 70 years old, from those who need a ventilator to those who have no symptoms at all. Our activities include holding social and study meetings, participating in academic conferences, publishing a newsletter, and providing consultation services for members. For the past 10 years, the association has also focused on advocacy activities, working with Diet members and others to make ongoing requests to the national government for the approval of new drugs and free newborn screening nationwide.
Figure 10.About the SMA Family Association
Subject 3: Value of Pharmaceuticals and its Evaluation
Dr. Tsutomu Goto, Professor, Graduate School of Business Administration, Keio University
Increasing Medical Expenses, Especially for High-Priced Drugs, Draws Attention
The increase in medical costs is a social issue, and expensive pharmaceuticals and medical technology are sometimes seen as problematic. According to data from the Federation of Health Insurance Associations (Kenporen), the number of monthly receipts of 10 million yen or more is increasing, but only a small percentage of cases are high-cost receipts. The total impact is about 40 billion yen, which is less than 1% of the total medical cost (about 5 trillion yen per year) of the Federation of Health Insurance Associations.
The Movement of Japanese Healthcare Expenditures
The following chart shows the trends in the ratio of medical care costs and pensions to GDP with respect to social security benefit costs ( Figure 11 ). Medical care expenditures here are defined slightly differently from national medical care expenditures, but include benefits from taxes and other sources other than insurance treatment, and do not include patient co-payments. Pensions have been stable since 2010 and have recently been declining. Health care spending increased until around 2010, but has not grown much in the second half of the 2010s, except during the Corona period. From a fiscal perspective, it is important that benefit costs are contained within the GDP growth rate because tax and premium revenues increase with GDP growth.
Figure 11. Movement of Medical Expenses (based on social security benefits)
Looking at the growth rates of medical expenditures, pensions, and GDP over time, both medical expenditures and pensions outpaced GDP growth in the 2000s. This indicates that the economy was experiencing low growth; in the 2010s, the growth rate of pensions calmed down due to the application of macro-sliding and other factors, but the growth of healthcare spending was still noticeable. Subsequently, medical costs increased further due to the corona.
Nominal GDP (GDP not adjusted for prices) is expected to grow 2-3% in the future. If healthcare spending grows by only 1%, it will be less than the growth in nominal GDP, which means that healthcare spending will be reduced in real terms. In addition, the demand for medical care will not increase significantly as the number of inpatients and outpatients is declining over the long term.
Considering the above, the increase in medical expenses is not necessarily a critical situation, and it is important to take time to discuss the allocation of such expenses. Of course, it is important to use medical expenses efficiently, so we need to consider what is a truly valuable drug.
Evaluating the value of pharmaceuticals
Efforts to evaluate the value of medical technologies, such as pharmaceuticals, and use them to inform policy and other decision-making are called Health Technology Assessment (HTA), and the value of medical technologies considered in HTA is expanding. I would like to emphasize that cost-effectiveness is only one axis of evaluation in HTA, and it is not the whole story. These are: health improvement value, economic value, and other value. One of the current challenges is that these values are not adequately taken into account.
How to evaluate diverse values?
For the evaluation of various values, we first present the elements of value and measure them. Next, the measured indicators are actually used in the evaluation of medical technology, and then the measured indicators are reviewed to ensure that they are more appropriately valued. This should be done jointly by all stakeholders, not just health economics experts. However, this is currently a challenge in Japan. Evaluation of diverse values is always ongoing, and just because it cannot be adequately assessed or quantified does not mean that it should not be considered.
The Value of Health Improvement, Economic and Otherwise
The value of health improvement is still being used in HTA for easily measurable indicators such as efficacy and safety, as well as for survival and some quality of life. However, it has been noted that this alone is not sufficient, and assessments are underway for wellbeing and capability as well.
As for the economic value, it includes the medical costs of treatment, public care costs, and the value (productivity) of the time of the patients and their families. The economic value is important not only to the patient and family, but also to the surrounding economy as a whole.
As for other values, various values have been proposed, and conceptualization is underway. There are many values that have not yet been quantified. For example, the "diffusion of science" effect, which has little effect on health improvement at present but will lead to cures in the future as medical technology develops, and the hope for small possibilities are proposed as value items.
Axis of valuation of medicines in HTA: summary of current status
Cost-effectiveness only evaluates part of the value of health improvement and economic value, and quantitative evaluation of other values is not yet available.
Regarding the "consideration" of diverse values in HTA, it is widely recognized that "cost-effectiveness" is only part of the diverse values. Values that are difficult to measure at this time are qualitatively "considered" in making decisions. Further case-by-case considerations are also made, and gradually the parties come to an agreement and "rules on considerations" may be made. Although cost-effectiveness can be quantified, I believe that everyone should be aware that there are limitations, and together we can improve the appropriateness and quality of decision-making.
Gene Therapy Drugs for SMA
In the UK, this gene therapy drug was recommended by the HTA agency about a year after it was approved. At that point, cost-effectiveness was uncertain and not calculated, but it was recommended because of its very significant effectiveness and value. A cost-effectiveness analysis was subsequently reviewed and a new assessment was made. Although not cost-effective, it was still judged to have significant value that could not be measured by cost-effectiveness and was recommended as a category of technology for rare diseases.
What else is being evaluated as an element of broad value?
Other values besides cost-effectiveness that can be quantified are gradually being evaluated, and qualitative values that cannot be quantified are also being actively taken into account.
More recently, the impact on family health (spillover effects) has been evaluated as a broad value component. Specifically, the impact of having to give up work due to nursing or caring for a family member (productivity impact) and the direct health impact of nursing or caring for a family member (quality of life impact) have been noted, and moves are underway to positively value these factors.
Panel Discussion
Facilitator : Kazuhiko Mori, Executive Director
Panelists: Dr. Reiko Arakawa, Dr. Yuko Oyama, Dr. Tsutomu Goto
Q．SMA治療の進歩の中、新たに生まれてきた課題について改めて教えてください。
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Mr. Arakawa
From the medical professionals' point of view, until now the only way to treat SMA was to monitor its progression, and what they could do, such as rehabilitation, was limited. However, there is now a significant increase in what needs to be done for SMA. Therefore, if there is a shortage of providers, even if there is a better treatment, it will not be able to reach patients. Especially in rural areas where there is a shortage of pediatric neurologists, the burden can be especially heavy, and it is important to secure the right people to take on this task. Furthermore, we need to support each other in this regard with an all-Japan team, and we need a different kind of collaboration and system than we have had in the past.
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Mr. Oyama
There are many real challenges. Because the challenges are perceived very differently before and after a cure is available, it is important to set priorities and ensure that they are solved one at a time. The top priority is to diagnose and treat the disease as early as possible, to get to the point where no one is left untreated, and to save lives. To achieve this, cooperation among various medical professionals is essential. Also high on the list of priorities are the additional medical care and rehabilitation necessary to ensure that children who have received treatment grow up healthy and well, as well as an understanding of their families and their own personal growth.
Q．早期診断とタイムリーな治療の重要性は理解しました。診断を迅速に行い、早期に最適な治療を行うことで効果が最大化される点について、価値評価の観点からポイントを教えてください。
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Mr. Goto
The value of early diagnosis and treatment is very high. This is also recognized in the fields of health economics and HTA. Our study investigated the relationship between school urine screening and early detection of IGA nephropathy and reported its value, including its cost-effectiveness; for SMA as well, the importance of early diagnosis and early treatment is clear and its value can be high. In general, too, the value assessment of early diagnosis and treatment is possible and an area in which progress is being made.
Q．SMAにおける早期診断と早期治療の重要性は理解しました。しかし、早期診断・早期治療を行った後でもケアが必要だというお話もありました。特に成人の患者さんや発症時期が遅れる方に対して、どのような点が重要だと考えているか教えてください。
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Mr. Arakawa
Of course, early treatment is extremely important. However, it is also important to lead children who are currently living with SMA to a better life. Early treatment may increase the number of patients with mild disease in the future, but currently there are many patients who require severe care. We need to consider the balance between promoting early treatment while firmly supporting the lives of patients currently undergoing treatment. Even within the family group, there is a difference in thinking between those who have undergone newborn screening and those who have already developed the disease.
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Mr. Oyama
Before and after the treatment, I feel as if I have a different disease. That is how wonderful the effects of the treatment are. However, if I dare to mention a challenge here, it is the importance of rehabilitation. Our members range in age from 0 to 70, and they all share the same challenge: the need for continued rehabilitation as well as treatment. Without rehabilitation, improvement is difficult and quality of life is difficult to improve. In particular, some parents of patients who received early treatment are reluctant to admit that their children have a genetic disease, and parents of children who have not yet developed the disease or have few symptoms may not be positive about rehabilitation. It is important to be aware of the intractable nature of the disease and to understand what it is and what symptoms it may cause. It is important to be aware of rehabilitation in a broad sense, even if it means preventing it from happening.
Q．リハビリの重要性についてはよく理解できました。価値評価の観点からはいかがでしょうか。
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Mr. Goto
The value of health improvement is not only in terms of vital and functional aspects, but also in terms of how it supports living and life. More specifically, how social support and care can have a positive impact on health improvement is valued. In order to evaluate these values, it is also important to find value together with medical professionals and patients' families.
Panel discussion
Finally
At this forum, we were able to share that new drugs have been introduced for SMA, which was once difficult to treat, and that newborn mass screening is beginning to spread in Japan, creating great hope for patients and their families. However, new challenges have also arisen along the way. In order to further advance these, I would like to take this opportunity to ask for your understanding and support.
The "Co-Creation intention" set forth in the Pharmaceutical Cooperative Industry Vision 2035 is that the key to solving problems is for everyone to work together to address complex social issues around the world. It is important that people from various walks of life have the opportunity to discuss and share at the same table. I hope that everyone will consider the meaning and value of having a variety of stakeholders participate in this forum, and I hope that this will lead to future developments.
(Masaaki Kozaki, Tomohiro Murakami, Takuro Matsuda, Industrial Policy Committee, Industrial Development Subcommittee)