“One shot of 700000”: a life-saving medicine for rare diseases

In the impression of Xing huanping, executive director of Beijing Meier spinal muscular atrophy care center, the rare disease SMA has not been so “widely concerned” for a long time.

the cause was a recent online “drug seeking” message. Wu Shiping, a 32 year old citizen in Huaihua City, Hunan Province, asked for help on the Internet. His son Xiaoyi, more than one year old, suffered from SMA, and needed to be injected with a special drug made in the United States, named nosignazon sodium, which costs about 700000 yuan per injection. However, according to we media, the drug is only sold in Australia at a $41, causing netizens to question the huge price difference.

on August 6, Bojian Biotechnology Co., Ltd., established in China by nosigna sodium R & D and manufacturer, publicly responded that the drug price was different from the patient’s out of pocket expenses after reimbursement, and the actual purchase price of the drug in the Australian government was $110000, but as it was included in the drug welfare plan of the country, the patient only had to pay a $41.

nosignazon sodium was approved to be listed in China for more than one year, and it is also the only SMA drug approved in China, which has not been included in the list of Medicare reimbursement drugs. Because of its high price and lifetime use, it is difficult to reach the hands of the vast majority of patients suffering from SMA.

However, in recent years, domestic public welfare foundations have launched patient assistance projects, and many provinces and cities have explored various forms of supplementary security modes to reduce the burden of SMA patients. Experts suggest that the “n + 1” mode should be carried out, including the reimbursement of basic medical insurance, and the cooperation of pharmaceutical enterprises, insurance companies, public welfare and charity organizations, so as to form a multi-level security network for rare disease treatment.

Meier SMA care center is a public welfare organization focusing on SMA patients and family support services in China. As early as last year, Xing huanping paid attention to Xiaoyi’s case.

on the afternoon of August 5, Xing huanping told the Beijing news that Xiao Yi’s parents had been working in Guangdong for a long time. After finding out that Xiaoyi was suffering from SMA in August last year, she was treated in many hospitals in Guangdong and Hunan, with poor results. With the deterioration of his condition, Xiaoyi has now been admitted to the ICU, using a ventilator and expectoration machine to maintain life.

public information shows that SMA is a rare autosomal recessive neuromuscular disease, which starts early, and some patients will attack within a few months after birth. After the onset of the disease, patients will gradually lose a variety of motor functions, including respiratory and swallowing functions. The disease incidence rate is about 1/6000-1/10000 in the newborn, regardless of sex and race. One of the 50 people in the general population is the carrier of the disease gene.

experts estimate that the number of SMA patients in China is about 20000-30000. Xing huanping said that since 2016, more than 1600 SMA patients have been registered in Beijing Meier SMA care center.

Based on the onset time and the maximum motor function, SMA patients are usually divided into four types. Xiaoyi is suffering from type I, which belongs to the most serious type of SMA. Tang Jihong, director of Neurology, children’s Hospital Affiliated to Soochow University, told the Beijing news that for type I patients, the most serious consequence of myasthenia is respiratory involvement. Once the ventilator fails to breathe, tracheal intubation is needed to assist breathing.

“if patients with type I are not treated, their natural survival time is generally recognized as 2 years old. Therefore, SMA is also known as the” number one killer of genetic diseases “in infants under 2 years old.” Xing huanping said.

in August this year, a study jointly compiled by Meier SMA care center and Shenzhen Research Institute of the Chinese University of Hong Kong showed that 64 of 181 patients with SMA – I had died. The average age at the time of death was 11.1 months, with a median of 8 months. 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 Province, is a child with SMA – Ⅱ. Zhezhe was born in February 2018. About a year later, Bao Jie found that his son suffered from muscle atrophy, dyskinesia, difficulty raising his hand and constipation. He could defecate only once in three or four days, and he had to use drugs to assist him.

Guo Jiani, a 26 year old Nanchang native, was found to have abnormal walking when she was 8 months old. She was diagnosed with SMA – Ⅱ at the age of 3 in Beijing. Over the years, she felt more and more weak in her legs. From the beginning, she could walk on the wall, and then she could not walk. Today, she needs help going to the bathroom and going to bed.

“SMA is a genetic disease that will not disappear with age or treatment, but will accompany the patient for life.” According to Tang Jihong, the general SMA – Ⅱ patients can reach the adult life span level, while the type Ⅲ patients can reach the normal life span level.

SMA was first discovered and reported in Austria in 1891. However, there has been a lack of effective treatment since then. “In the absence of specific drugs, patients mainly through nerve nutrition drugs and exercise rehabilitation training to delay the degradation of body function.” Tang Jihong said.

since she was 3 years old, Guo Jiani reported to the rehabilitation center nearby every day. There, every day, she repeatedly pressed her legs, stood up and sat down, pushed the walker to walk and so on. In addition to taking hormone drugs, her legs gradually gained some strength. She had to give up the hormone, but her hands were itchy after three months.

after that, Guo Jiani also tried various treatment methods, such as acupuncture, drinking Chinese medicine, using back and back, and various strange therapies, but none of them had any effect. At the age of 9, she was in an electric wheelchair.

song Qian, head of Jiangsu SMA patients’ organization, told the Beijing news that in the early stage, domestic patients had limited understanding of SMA, and most of them learned nursing knowledge through patients’ organizations. Generally, families will give their children massage, massage, swimming, AIDS exercise, home equipped with expectoration machine, stand stand, chair, etc., the earliest in China even the lack of expectoration machine, the need for overseas shopping.

in December 2016, nosignazon sodium injection developed by Bojian biology was approved by the food and Drug Administration of the United States, becoming the first specific drug in the world to treat SMA. According to the official website of Bojian, as of August 2019, the drug has been listed in more than 50 countries and regions.

on April 28, 2019, nosignazon sodium was approved for marketing in China, becoming the first and only specific drug for SMA treatment in China. In addition, two SMA drugs, zolegnsma of avexis, a subsidiary of Novartis, and risdiplam of Roche, are not yet available in China.

Tang Jihong is zhezhen’s attending doctor. He has injected nosignazon sodium for many SMA patients including zhe Zhe. According to his observation, the drug treatment effect is more obvious, the patient’s muscle strength is improved. Zhe zhe couldn’t even hold the bottle before. After treatment, he could grab the bottle and drink milk. The other two patients had more strength to write and brush their teeth. Among them, a 16-year-old patient who is studying in high school usually needs to sit in a wheelchair, and can help stand for half an hour after treatment.

However, Tang Jihong also said that nosinogenase sodium is not a miracle drug, which can not completely restore the patients to the level of normal people, let alone cure SMA. He told the Beijing news that “the most important role of nosinogenase sodium is to delay degradation. For example, it may take one or two years to degrade without drugs, but it may take 10 years to use drugs.”

after learning about the price of raw sodium nosina, Guo Jiani was poured cold water. “It’s really too expensive. It’s very far away for me. It’s impossible to incorporate this into my life planning.”

according to the official website of Bojian biology, in China, the single price of nosinasheng sodium injection is close to RMB 700000. Patients need 5-6 injections in the first year, and then 3 doses a year thereafter, possibly for life. That is to say, if the patient is diagnosed at 3 years old and lives to 50 years old, according to the injection frequency and price mentioned above, it will cost 102.9 million yuan at his own expense.

song Qian said that there were about 100 patients in her group of patients, and only three or four of them used nosignazon sodium. Even if they had been used, they were worried that it would not be sustainable in the future.

Tang Jihong said that in clinical practice, many parents want to use nosigna sodium for their children, but “they frown as soon as they hear the price.” Only a small number of people choose to inject, “first, the family’s economic conditions are relatively good, and they can bear it; second, parents think that with the development of medicine, there may be medicine to replace this medicine in the future, and use this medicine to maintain the drug first, so as to delay the degradation; third, wait for policy changes, such as reimbursement.”

for the few patients who use nosignazon sodium, Tang Jihong will be more careful when injecting. “It needs multi-disciplinary consultation, such as orthopaedic surgery, imaging and neurology, and even finding the puncture point under CT images, and injecting drugs into the spinal cord.” Tang Jihong said, “a bottle of nuoxinasheng sodium injection is 700000, only 5ml, 20 drops per ml, that drop of medicine is 7000 yuan, a drop of inaccurate is a waste.”

not only in China, but also in foreign countries, the price of nosigna sodium is “skyrocketing”. In the United States, according to the former Bojian bio’s public statement, the single price of nosinogenase sodium is US $125000, about 20% higher than the price of 700000 yuan in China. In Australia, the price of the drug purchased by the government is $110000 per unit, which is also very high.

“the rare disease drugs are mostly molecular biological drugs with high R & D costs and a small consumer group, so the pricing is generally high.” Zhang Xiao, director of the medical insurance and social security research center of Southeast University, told Beijing News.

zolegnsma, another kind of SMA treatment drug, is known as “the most expensive drug in the world” because its price is more than 10 million yuan.

a researcher from the domestic medical insurance system said that at the stage of drug listing, the pricing is determined by the enterprises themselves. After the national development and Reform Commission abolished the maximum retail price limit of drugs in 2014, if the drugs are not included in the medical insurance, the pricing decisions are basically “more market-oriented”.

in order to cure his son, Wu Shiping launched crowdfunding on the Internet in July 2020. He told the media, “a needle of 700000 yuan, with the current income, do not eat or drink dry for 12 years to buy a special drug.”

at noon on August 10, a reporter from Beijing News saw on a fund-raising platform that Wu Shiping’s fund-raising on July 19 had raised more than 300000 yuan, but it was still far from the goal of 700000 yuan. Even if it is raised to 700000, it is only the first injection cost, which is still a drop in the bucket.

according to Chen Wu, head of SMA patients’ organization in a central province, network crowdfunding can not completely solve the problem. Because SMA is a disease that requires lifelong medication, “it’s impossible to crowdfunding every time there’s an injection.”

However, although the price of nosilan sodium is “skyrocketing” abroad, Xing huanping said that in most countries and regions that have been approved for listing, the drug has been fully or partially reimbursed, including Japan, South Korea, Taiwan and Hong Kong in Asia.

recently, we media claimed that the injection of the drug in Australia only costs a $41. On August 5, Bojian biology responded to the Beijing News reporter that the drug price and the patient’s out of pocket expenses after reimbursement are completely different concepts. The price of the drug purchased by the Australian government was $110000, while the $41 was the patient’s out of pocket expenses.

the Beijing News reporter inquired the official website of the Ministry of health of the Australian government and confirmed that the injection of sodium nosinogenase was carried out