In the impression of Xing Huanping, executive director of the Beijing Meier Spinal Muscular Atrophy (SMA) Care Center, the rare disease SMA has not received so much attention as it is now.
The cause is a recent online "seeking medicine" message. Wu Shiping, a 32-year-old citizen from Huaihua City, Hunan Province, asked for help online. His 1-year-old son, Xiao Yi, has SMA and needs to be injected with an American-produced Nocina The price of an injection of sodium is about 700,000 yuan. However, some self-media said that the drug is only sold for 41 Australian dollars (equivalent to about 206 yuan) in Australia, and the huge price difference has caused netizens to question.
On August 6, Bojian Biotechnology (Shanghai) Co., Ltd. (hereinafter referred to as Bojian Bio), established in China by the R&D and manufacturer of Nosinagen Sodium, publicly responded that the price of the drug is different from the patient’s out-of-pocket expenses after the reimbursement of the drug. The actual price of a single purchase by the Australian government is 110,000 Australian dollars (equivalent to approximately 550,000 yuan), but because it is included in the country’s drug welfare plan, patients only need to pay 41 Australian dollars.
Nosinagen sodium has been approved for marketing in my country for more than a year, and it is also the only approved SMA drug in China. It is currently not included in the list of medical insurance reimbursement drugs. Due to its high price and lifetime use, it is difficult to reach the vast majority of SMA patients suffering from illness.
However, in recent years, domestic public welfare foundations have initiated patient assistance projects, and many provinces and cities have explored various forms of supplementary protection models to reduce the burden on SMA patients. Experts suggest that the "N+1" model should be implemented, which includes both basic medical insurance reimbursement, as well as the cooperation of pharmaceutical companies, insurance companies, and charitable organizations to form a multi-level rare disease treatment protection network.
Noxinasheng Sodium Injection. Source: Bojian Company's official website
"The number one genetic disease killer" for infants under 2 years old
Meier SMA Care Center is a non-profit organization focusing on domestic SMA patients and family support services. As early as last year, Xing Huanping paid attention to Xiaoyi's case.
On the afternoon of August 5, Xing Huanping told a reporter from the Beijing News that Xiaoyi's parents worked in Guangdong for many years. After finding that Xiaoyi was suffering from SMA in August last year, he was treated in many hospitals in Guangdong and Hunan with poor results. As the condition continues to deteriorate, Xiaoyi is now admitted to the ICU, using a ventilator and expectoration machine to maintain his life.
Public information shows that SMA is a rare autosomal recessive genetic neuromuscular disease with an early onset, and some patients will have it within a few months of birth. After the onset, the patient will gradually lose various motor functions, including breathing and swallowing. Regardless of gender and race, the disease has an incidence of about 1/6000-1/10000 in newborns, and one out of 50 ordinary people is a carrier of the pathogenic gene.
Some experts estimate that the number of SMA patients in China is about 2-3 million. Xing Huanping introduced that since 2016, more than 1,600 SMA patients have been registered in Beijing Meier SMA Care Center.
Based on the time of onset and the maximum motor function that can be achieved, SMA patients are usually divided into 4 types (I, II, III, IV). Xiao Yi suffers from type I, which is the most serious type of SMA. Tang Jihong, director of the Department of Neurology at the Children’s Hospital of Soochow University, told reporters from the Beijing News that for type I patients, the most serious consequence of muscle weakness is breathing involvement. Once the ventilator "cannot breathe", the tracheal intubation is necessary to assist breathing. .
"Type I patients, if they are not treated, the natural survival time is now recognized as 2 years old. Therefore, SMA is also known as the'top genetic disease killer' for infants under 2 years old." Xing Huanping said.
In August this year, the "White Paper on Survival and Challenges of SMA Patients in China-Based on the American Pediatric Patient Registration Database" jointly compiled by the Meier SMA Care Center and the Shenzhen Research Institute of the Chinese University of Hong Kong showed that of the 181 follow-up SMA-I patients, There are 64 people who have died. The average age at the time of death was 11.1 months, the median was 8 months, and the mortality rate was as high as 35%.
Even for patients with other types of SMA with relatively low severity, the survival status is not optimistic. Zhezhe, the son of Bao Jie from Suqian, Jiangsu, is a child with SMA-Ⅱ. Zhezhe was born in February 2018. About a year later, Bao Jie discovered that his son had problems such as muscle atrophy, exercise difficulties, difficulty raising his hands and head, and constipation. He often had a bowel movement every three or four days, and he must be assisted by drugs.
Children with SMA undergo rehabilitation training under the guidance of a doctor. Photo courtesy of respondents
Guo Jiani, a 26-year-old from Nanchang, was found to be walking abnormally when she was 8 months old. She was diagnosed with SMA-Ⅱ at the age of 3 in Beijing. Over the years, she felt that her legs were getting weaker and weaker. From the very beginning, she was able to walk on the wall, and then gradually unable to walk. Today, she needs assistance to go to the bathroom and bed to rest.
"SMA is a genetic disease that will not disappear with age or treatment, and will accompany the patient for life." Tang Jihong introduced that in general, SMA-Ⅱ patients can reach adult life expectancy (over 18 years), while type III can reach Normal life expectancy.
In 1891, SMA was first discovered and reported in Austria. However, there has been a lack of effective treatment options since then. "Before there was no special medicine, patients mainly used nerve-nutrition medicine and sports rehabilitation training to delay the deterioration of body function." Tang Jihong said.
From the age of 3, Guo Jiani reported to the rehabilitation center near her home every day. There, she repeated the actions of pressing her legs, standing up and sitting down, and walking with the walker every day, plus taking hormone drugs, her legs slowly gained some strength. But in less than three months, her hands were covered with hair due to the use of hormones, and her skin became extremely itchy, so she had to give up.
After that, Guo Jiani also tried various treatments, such as acupuncture, drinking Chinese medicine, using back and back, "and all kinds of strange treatments", but they were not effective. When she was 9 years old, she was in an electric wheelchair.
Song Qian (pseudonym), head of the Jiangsu SMA patient organization, told the Beijing News that in the early days, domestic patients had limited understanding of SMA, and most of them learned nursing knowledge through patient organizations. Generally, families will give children massage, massage, swimming, and exercise aids. There are expectoration machines, standing frames, and posture correction chairs at home. At the earliest, even the expectoration machines were lacking in China, and they needed overseas shopping.
In December 2016, Bojian Bio-Research and Development of Noxinagen Sodium Injection was approved by the U.S. Food and Drug Administration (FDA) and became the world's first specific drug for the treatment of SMA. According to Bojian’s official website, as of August 2019, the drug has been listed in more than 50 countries and regions.
On April 28, 2019, Nosinagen Sodium was approved for marketing in China, becoming China's first and only specific drug to treat SMA. In addition, there are two SMA drugs-Novartis subsidiary AveXis' Zolegnsma and Roche's Risdiplam, but they are not yet on the market in China.
Tang Jihong is Zhezhe's attending doctor. He has injected Noxinagen sodium for many SMA patients including Zhezhe. According to his observation, the drug treatment effect is more obvious, and the patient's muscle strength is improved. Zhezhe could not even hold the baby bottle before. After the treatment, he could grab the baby bottle and drink milk by himself. The other two patients had more energy to write and brush their teeth. Among them, a 16-year-old patient in high school usually takes a wheelchair to go to school and can stand for half an hour after treatment.
However, Tang Jihong also said that Noxinat is not a magic drug, and it cannot restore the patient to a normal level, let alone cure SMA. He told a reporter from the Beijing News that the main effect of Nosinagenic Sodium is to delay degeneration. For example, it may take one or two years to degrade to a serious degree without medicine, but it may take 10 years.
Children with SMA undergo rehabilitation training under the guidance of a doctor. Photo courtesy of respondents
"Sky price" at home and abroad
After learning about the price of Nosina's raw sodium, Guo Jiani was poured cold water, "It's really too expensive, it's very far away for me, it's impossible to incorporate this matter into my life plan."
According to Bojian's official website, in China, the price of noxinagen sodium injection is close to RMB 700,000. Patients need to inject 5-6 doses in the first year, and then 3 doses every year thereafter, and may need to inject the drug throughout their lives. In other words, if the patient is diagnosed at the age of 3 and the life expectancy reaches 50 years old, according to the above-mentioned injection frequency and price, it will cost 102.9 million yuan at full expense.
Song Qian said that there are about 100 patients in her patient group, and only three or four use Nosina sodium. Even if it has been used, she is worried that it will not be sustainable in the future.
Tang Jihong said that in clinical practice, many parents want to use Nosina sodium for their children, but "the price immediately frowns at the price." Only a few people choose injections. "First, the family's economic conditions are better and they can afford it; The second is that parents think that with the development of medicine, there may be a (cheap) medicine to replace this medicine in the future, and use this medicine to maintain it first to delay the deterioration; the third is to wait for policy changes, such as reimbursement."
For the few patients who use Noxinarine Sodium, Tang Jihong takes extra care when injecting. "Orthopedic surgery, imaging, neurology and other multidisciplinary consultations are needed, and even the puncture point must be found under the CT image to inject the medicine into the spinal cord." Tang Jihong said, "A bottle of Nosinagen Sodium Injection is 700,000 yuan, There are only 5 milliliters, 20 drops per milliliter, and that one drop of medicine is 7,000 yuan. A drop of medicine is wasteful."
Zhezhe, two and a half years old, is a child with SMA-Ⅱ and uses a standing frame to assist in training. Photo courtesy of respondents
Not only in China, but also in foreign countries, the sodium produced by Nosina is also "sky price". In the United States, according to the previous public statement of Bojian Biologics, the single price of Nosina Sodium is US$125,000 (equivalent to approximately RMB 870,000), which is about 20% higher than the single price of 700,000 RMB in China. . In Australia, the government purchases the drug at a price of 110,000 Australian dollars (equivalent to approximately 550,000 yuan), which is also very high.
"Most rare disease drugs belong to molecular biology pharmaceuticals, with high R&D costs, coupled with a small consumer group, so the prices are generally higher." Zhang Xiao, director of the Medical Insurance and Social Security Research Center of Southeast University, told the Beijing News reporter.
Zolegnsma, another drug for the treatment of SMA, is called the "world's most expensive drug" because its price is equivalent to more than 10 million yuan.
A researcher on the domestic medical insurance system said that the company decides the price of a drug at the launch stage. After the National Development and Reform Commission abolished the maximum retail price of drugs in 2014, if drugs are not included in medical insurance, pricing decisions are basically "comparatively market-oriented."
In order to treat his son, in July 2020, Wu Shiping launched a crowdfunding campaign on the Internet. He told the media, “With the current income of 700,000 yuan per injection, you can buy a special medicine for 12 years without eating or drinking.”
At noon on August 10, a reporter from the Beijing News saw on a fundraising platform that Wu Shiping’s fundraising initiated on July 19 had raised more than 300,000 yuan, but the goal of 700,000 was still far away. Even if it is 700,000, it is only the cost of the first shot, and it is still a drop in the bucket.
According to Chen Wu, the head of the SMA patient organization in a central province, online crowdfunding cannot completely solve the problem. Because SMA is a disease that requires lifelong medication, “it’s impossible to crowdfund every time it’s time for an injection.”
SMA-I patient Xiao Yi raised funds on a certain platform. Screenshot from a fundraising platform
It is expected to lower the price after being included in medical insurance
However, although the sodium produced by Nosina is also "sky price" abroad, Xing Huanping said that in most countries and regions that have been approved for marketing, the drug has been fully or partially reimbursed, including Japan, South Korea, Taiwan, China, China Hong Kong.
Regarding the recent self-media claim that injecting the drug in Australia only costs 41 Australian dollars, on August 5, Bojian Biological responded to the Beijing News reporter that the price of the drug and the patient out-of-pocket expenses after the reimbursement of the drug are two completely different According to the concept, the Australian government purchases the drug at a price of 110,000 Australian dollars (equivalent to approximately 550,000 yuan), and 41 Australian dollars (equivalent to approximately 206 yuan) is the patient’s out-of-pocket expenses.
A reporter from the Beijing News inquired on the official website of the Ministry of Health of the Australian Government and confirmed that Nosinagen Sodium Injection was included in the country’s Pharmaceutical Benefits Plan (PBS) on June 1, 2018. The website showed that the single drug price was 110,000 Australian dollars. The patient’s out-of-pocket expenses after reimbursement are up to A$41.
The official website of the Australian Government’s Department of Health shows the price of Nocinasheng Sodium Injection.
In mainland China, noxinagen sodium is not included in the list of medical insurance reimbursement drugs. Li Yangyang, executive director of Ai Kunwei Enterprise Management Consulting (Shanghai) Co., Ltd., who has been concerned about rare diseases in China for many years, told the Beijing News that as of now, 38 rare disease drugs have been included in the medical insurance catalog, and 26 have been listed. Rare disease drugs are not included, and more than half of these are for annual treatment costs of more than 500,000. There are 6 kinds of rare disease drugs as "super high-value drugs", and noxinagen sodium is one of them.
On August 6, Bojian Bio responded that according to relevant regulations, the drugs participating in the 2019 national medical insurance negotiations must be drugs approved for marketing before December 31, 2018. Nosina sodium was approved in February 2019, so it did not participate in the 2019 national medical insurance negotiations.
According to the official website of the National Medical Security Administration, on August 3, the "2020 National Medical Insurance Drug Catalog Adjustment Work Plan" was launched. After enterprise declaration, expert review, negotiation and bidding, drugs that meet the requirements can be included in the 2020 medical insurance drug catalog.
On August 5, Bojian Company stated to the Beijing News that the company is actively preparing to submit the information of Noxinagen Sodium to the Medical Insurance Bureau. If the drug passes the expert review, it will enter the medical insurance negotiation link. If it is determined to be included in the 2020 national In the list of medical insurance drugs, patients are expected to purchase at a lower price.
However, a number of interviewed experts analyzed by reporters from the Beijing News that the inclusion of rare disease drugs into medical insurance is a very complicated process, due to uncertainties in the number of patients, conditions, and drug efficacy of rare diseases, and the price of rare disease drugs High but few people benefit. If covered by the medical insurance fund, whether it will impose a heavier burden on the medical insurance fund, whether it is unfair to others, etc., are all practical considerations. Therefore, it is still unknown whether Noxinagen sodium will be included in medical insurance.
Even if included in medical insurance, medical insurance funds may not cover the full cost of using the drug. The above-mentioned domestic medical insurance system researchers told the Beijing News that according to the different levels of economic development and medical insurance fund support in various regions in China, the annual reimbursement ceiling for basic medical insurance is between 10,000 and 300,000, with a median value of 18. About ten thousand. "That is to say, even if the medicine is entered into the medical insurance catalog, patients in areas with general economic levels may only be reimbursed by medical insurance for 180,000 yuan. Even in areas with the most abundant medical insurance funds, patients can only receive a maximum of 300,000 yuan for reimbursement. "
Faced with the huge gap in treatment costs at home and abroad, many families of patients choose to work in the United States, Japan and other places, "just to seek almost free treatment." Song Qian said that he is not Japanese, but works or studies in Japan and holds 6 Children of foreign nationals who have valid visas for more than one month and participate in the National Health Insurance can also receive the same medical insurance for Nosina sodium as Japanese nationals. Someone around her specializes in cooking for their children and then goes to Japan to work chef.
Multi-party cooperation and rare disease treatment guarantee network
Although mainland China has not yet included Nosinagen Sodium Injection in the medical insurance list, in many provinces and cities, some public welfare foundations have launched assistance projects to reduce the burden on SMA patients.
In November 2019, Zhezhe injected Nocinagen sodium at the Children's Hospital of Soochow University. He also became the first child in Jiangsu Province to receive the drug.
In November 2019, Zhezhe injected Nocinagen sodium at the Children's Hospital of Soochow University. Source: WeChat official account of Children's Hospital of Soochow University
According to Tang Jihong, Zhezhe accepted an assistance program for patients with SMA. The first 4 injections were “one get three free”, that is, patients only need to pay 700,000 yuan for the first injection; in the subsequent maintenance phase, every 4 months One shot, "one shot gets one shot" is equivalent to 350,000 yuan per shot.
Bojian Company introduced to the Beijing News reporter that the above-mentioned project is an SMA patient assistance project launched by the China Primary Health Care Foundation on May 31, 2019. The treatment cost for the patients receiving assistance in the first year is about 1.4 million yuan, which can save about two-thirds compared with full self-finance; after that, the annual treatment cost is about 1.05 million yuan, which can save about half compared with full self-finance. . Up to now, more than 80 SMA patients across the country have received medication with the help of this assistance project.
Public information shows that the China Primary Health Care Foundation was established in 1996 with the approval of the Ministry of Civil Affairs. It is a national public fundraising foundation sponsored by the China Peasants and Workers Democratic Party and managed by the National Health Commission.
According to its official website, the foundation has cooperated with Bojian to prepare patient assistance projects to help SMA patients reduce the payment burden and improve the accessibility of treatment. It has been launched in 14 provinces and cities across the country, and the first phase covers 25 central hospitals.
On August 7, China Primary Health Care Foundation. Photo by Beijing News reporter Li Yun
On August 7, a staff member of the Project Department of the China Primary Health Care Foundation told the Beijing News that the funding source of the foundation is mainly donations from pharmaceutical companies and social charities. The assistance for rare diseases such as SMA is part of the foundation's "Oasis of Life" patient assistance charity project. The recipients are mainly patients with serious diseases and rare diseases who bear high-priced drugs. The treatment costs are funded by the foundation, and the pharmaceutical companies give benefits to the patients. Appropriate payment and other parties are jointly responsible.
In addition to receiving assistance from the China Primary Health Care Foundation, Zhezhe also received assistance from the Jiangsu Charity Federation. “It costs 700,000 yuan for an injection, and you can get a reimbursement of 150,000 yuan,” said Zhezhe’s father, Bao Jie. .
In a province in the central region where Chen Wu is located, a certain percentage of reimbursement for sodium nucleoside can also be given. According to Chen Wu, there are currently about 10 patients in the province who have used Noxinarine Sodium, and one shot can be reimbursed about 600,000 yuan.
A reimbursement form for SMA patients in a province, the medical insurance of Nosina Sodium is about 600,000 yuan. Photo courtesy of respondents
According to the "China Rare Disease Medical Insurance City Report 2020" jointly released by the Center for Rare Diseases and IQVIA Management Consulting Team in May this year, there are seven modes of supplementary protection for rare diseases in addition to medical insurance in China: Special fund model, critical illness negotiation model, financial contribution model, policy-based commercial insurance model, medical assistance model, medical insurance sporadic supplement model, and independent declaration model.
Li Yangyang, the lead researcher of the report, introduced to the Beijing News reporter that the above-mentioned successful cases of SMA reimbursement in a certain province in central China should belong to the sporadic supplementary model of medical insurance. "This province has not previously introduced a provincial-level institutionalized rare disease protection policy. SMA patients Successful reimbursement is equivalent to an example of individual case assistance."
Both Li Yangyang and Zhang Xiao said that the rare disease protection plan that all walks of life are looking forward to is the implementation of the "N+1" model. "1" refers to the reimbursement of rare diseases by basic medical insurance, and "N" refers to the supplementary assistance policy jointly cooperated by the government, pharmaceutical companies, insurance companies, charity organizations and other parties. At present, these policies are being carried out experimentally in various parts of the country. In the future, it is expected to realize a multi-pilot and multi-level rare disease treatment guarantee network at the national level.
On August 7, the relevant person in charge of the health department of Hunan Province also said in an interview with Xinhua News Agency that to truly solve the problems of difficult and expensive medication for rare diseases, it is necessary to actively develop commercial insurance and comprehensively utilize social resources such as charity and relief to provide patients. To reduce the burden, the relevant departments should also speed up the research and development and consistency evaluation of generic drugs to fundamentally improve the availability of related drugs.
The National Medical Security Administration stated in its reply to the CPPCC member’s proposal at the end of 2019 that, in general, the current system has included some rare disease drugs in the basic medical insurance drug list, and has provided rare disease patients with medical assistance. . In the next step, the National Medical Insurance Bureau will take into account the drug needs of the insured persons, medical insurance financing ability and other factors, and through rigorous expert review, gradually include the rare disease drugs with definite curative effect and the medical insurance fund can bear into the medical insurance payment scope.
Beijing News reporter Xiang Kai Li Yun intern Wu Xiaoxuan