The breakthrough of rare disease families: Fighting for drugs for children for many years, the only drug is facing delisting
The 3-year-old half-end obediently lay on the hospital bed that was larger for him, the hanging needle pierced into the skin, and the ECG real-time monitoring device was attached to him, and the cables of the instrument were scattered in the corner of the bed. For more than a year, he quickly adapted to the life of weekly injections, and has stopped crying or making trouble, and his father said that this is entering "energy", and he also chose to believe.
A year and a half ago, a terminal terminal from Zhejiang was diagnosed with the rare disease mucopolysaccharidosis IVA. "Weimingzan", produced by Biomarin Pharmaceutical Inc., a US pharmaceutical company, is currently the only drug suitable for disease remission in patients with rare disease type IVA.
However, in May next year, the drug will be withdrawn from the Chinese mainland market. In June this year, pharmaceutical companies responded to Nandu and N video reporters that the company had decided not to renew Weimingzan's import drug registration certificate in China, and the current import drug registration certificate will expire in May 2024.
Without medicine, what will happen in the future? Li Xiaoli, a parent of a child in Guangzhou, has been thinking about this question recently. She told the Nandu reporter in confusion, "If the drug is stopped, the only possible hope for us is gone." ”
The end end is being treated with injections.
Trapped growth
"We loved her so much and it was hit hard." Li Xiaoli couldn't figure out why "this rare plot like a TV series will happen to her own children" because she is just an ordinary person living an ordinary life. During the interview, she couldn't help but cry and told the Nandu reporter that this was almost the darkest moment of her life, and there was nothing more difficult to accept.
About a year ago, Li Xiaoli discovered the difference between her daughter Tongtong and children of the same age, "She has always been not very tall, and her athletic ability is relatively weak. At first, I thought it was just a small problem, but unexpectedly, after the examination, Tongtong was diagnosed with a rare disease that Li Xiaoli's family had never heard of before - mucopolysaccharidosis IVA.
Even with all the best treatment, the disease has gradually eroded Tongtong's young body during this year: her legs are slowly deformed, her walking is still unstable, and after taking off her clothes, you can see obvious rib valgus... She was supposed to go to kindergarten, but she had not yet found a suitable school.
After the illness, Tongtong's growth seems to be "retreating".
"Maybe for other children, in the process of growth, their self-care ability will slowly increase, but she can't do it." In the face of the child's plight, Li Xiaoli often feels painful and powerless, "Children like them, the bones are relatively fragile, so although you intend to teach her, she also intends to learn, but she really can't make it." ”
Li Xiaoli does not want her child's life to be trapped by illness and bound by a degraded body, but to live a quality life.
In October 2019, Luo Zhou, a native of Zhejiang, was surprised to welcome the birth of his child Duanduan. Until the age of one and a half, the child was not abnormal until his height stopped at 83 cm. At the same time, he found that the child was still a little kyphosis, always hunched over, and walked slowly.
After the examination, the doctor told Luo Zhou that the end end was not only kyphosis, but also hip dysplasia. In the long period that followed, Luo Zhou and his son began to go to the hospital frequently, but they were only doing orthopedic examinations and treatment. He customized two braces for the child, but the child was more likely to fall when he walked with an unstable center of gravity, and one of the braces to treat the spine was left unused.
Half a year later, Duanduan's situation did not improve significantly, Luo Zhou hung up the number of Zhejiang University Children's Hospital, and under the doctor's advice, took Duanduan to do genetic testing, and was diagnosed with mucopolysaccharidosis type IVA soon after. "This rare disease is very serious in the end, the lifelong height is only about 1.2 meters, the child can still walk in elementary school, junior high school may need crutches, may have to use a wheelchair in the future, and even the life expectancy is shorter." Luo Zhou did not dare to imagine that since entering the patient group, several children about nine years old in the group had passed away.
Zou Chaochun, chief physician of the Department of Endocrinology of the Children's Hospital Affiliated to Zhejiang University School of Medicine, introduced to Nandu reporters that mucopolysaccharidosis (MPS) is a group of genetic rare diseases with congenital metabolic abnormalities. The lack of lysosomes in the patient's body cannot decompose mucopolysaccharides, so that mucopolysaccharides are continuously deposited in the body, which will cause damage to the bones and organs of the patient's whole body, and even affect the patient's life.
"Recently, new symptoms have been discovered, and mucopolysaccharidosis should currently be divided into 8 types, and the symptoms will vary depending on the type." Zou Chaochun told the Nandu reporter that the patient was born with not much mucopolysaccharide in the body, so it looked no different from ordinary people, but as the body grew, symptoms such as slow walking and bone deformation appeared.
In the words of the patient's family, mucopolysaccharidosis IVA is a rare form of rare disease. Enzyme replacement therapy has become the most suitable choice for most patients with type IVA, Zou Chaochun explained, this treatment method is to supplement the missing enzymes used to degrade mucopolysaccharides in the patient's body to alleviate the disease. The only applicable drug for mucopolysaccharidosis IVA is Vimizim (elosulfase alfa), but the choice of medication is a lifelong thing, and patients are treated by drug injection for life.
Zou Chaochun introduced that another treatment is hematopoietic stem cell transplantation, under the premise of enzyme replacement therapy, in most cases it is not recommended to transplant patients with type IVA, which may be more risky.
The only drug is about to be delisted
In addition to medication, Li Xiaoli didn't know what else to do to help her child, "It's very heartbreaking, it seems that there is not much that can be done for her." ”
About two months after her daughter Tongtong was diagnosed, she used Wei Mingzan, and the drug was injected into her young body. According to the patient's weight, a bottle of 5 ml of medicine is needed for every five pounds, 7500 yuan per bottle, and injected once a week. Today, Tongtong needs 6 bottles of medicine at a time, and 45,000 yuan for weekly injections.
Li Xiaoli estimates that if she takes medicine every week, Tongtong's drug cost will be as high as more than two million yuan a year. She explained that when she first started using drugs in 2022, pharmaceutical companies had drug gifts, as long as they paid 500,000 yuan a year, other drugs could be used, but now the drug gift discounts have also been canceled. Even if you can reimburse one million through the "Suisaikang" insurance, you will have to pay more than one million out of pocket.
Tongtong took medication intermittently, and also stopped taking drugs due to the epidemic in the middle. Every time I go to the hospital to take medicine and drip drips, it takes six or seven hours. Throughout the day, Li Xiaoli was fully focused on Tongtong, "The child's injection is actually not very cooperative, and it depends on the drip rate when taking medicine." ”
But the drug finally delayed the erosion of the disease, she felt that after taking the drug, the child's physical strength would become better, although there was still a gap with children of the same age, but the height was no longer stagnant.
However, soon after, Li Xiaoli heard the rumors that Wei Mingzan was going to be delisted.
Many family members of type IVA patients told Nandu reporters that Weimingzan, produced by Biomarin Pharmaceutical Inc., a US pharmaceutical company, is currently the only drug suitable for disease remission in MPS IVA patients.
"Children have already spent so much energy and money on medication, and if they stop taking medicine, it is equivalent to losing their previous achievements, which will have a great impact on them." Li Xiaoli thinks about what to do in the future every day, and she said confusedly, "If the drug is stopped, the only possible hope for us is gone." ”
"Let children use medicine" is also the original intention of Zhengyu Mucopolysaccharide Rare Disease Care Center, Zheng Yu, who founded this organization. In order to allow Wei Mingzan to enter the Chinese mainland market, she also chased to the United States.
Zheng Yao's daughter is also a mucopolysaccharidosis IVA patient, in order to seek medicine for her daughter, she has been running around for many years, and learned that a pharmaceutical company in the United States has developed a special drug, so she "flew" to the United States. Until Wei Mingzan was approved for marketing in the United States, she tried to contact pharmaceutical companies for negotiations, hoping to let domestic children also use special drugs.
"The power of one person is too small to have no sound." Zheng Yu told the Nandu reporter, "I wondered if we could also unite together, face this disease together, appeal to all sectors of society, attract attention, and finally have social security to support children to use medicine." ”
Nandu reporter inquired and learned that in November 2018, the Drug Evaluation Center of the State Medical Products Administration issued the Notice on Releasing the First List of Urgently Needed Overseas New Drugs for Clinical Purposes, and Weimingzan is on the list. It is reported that the drug was first approved for marketing in the United States in 2014.
In 2019, Zheng Yao finally waited for Weimingzan, but he did not expect to experience the "delisting" of drugs in just a few years. "At the time, I thought I had survived our most painful years, but now there is just a little hope, and the pharmaceutical company has abandoned us again."
In June this year, in response to the delisting of drugs, Nandu reporters contacted pharmaceutical companies to further understand the situation. BioMarin Pharmaceutical responded to Nandu reporters that the company has decided not to renew the registration certificate of imported drugs in China, and the current import drug registration certificate will expire in May 2024.
"Complex market access structures make it unsustainable for certain drug supplies, particularly for the treatment of rare diseases," the company said. In the past few years, we have done our best to discuss viable reimbursement opportunities for Vimingzan, but with little success, we have decided not to continue to register the marketing license for this product. "In addition, the company is exploring ways to provide patients currently receiving treatment with a continuous supply of medications.
The second "lifesaver"
"Actionable reimbursement opportunities" are also what parents are desperately seeking. In addition to medication, medical insurance is the second "lifesaver" for families with rare diseases.
Zhang Yuping, who lives in Zhejiang, is an early parent in China who started to use medicine for her children, so she did not hesitate to spend high drug costs, and letting Weiming praise into medical insurance was one of the important reasons for her insistence on medication.
In July 2019, Zhang Yuping's child was diagnosed with mucopolysaccharidosis type IVA, and heard that the treatment drug Weiming agreed that it had been listed in China, although the price was high but it was likely to enter Zhejiang Medical Insurance, after repeated weighing, she still decided to find other treatment channels for her child while waiting for good news from medical insurance.
"During that time, my mood was very low, as long as I had time, I would go to the hospital, Beijing, Shanghai, Chinese medicine, Western medicine, I took my children to see it. I kept trying, I kept weighing, I thought about stem cell transplantation, I thought about gambling, and finally I gave up. ”
Zhang Yuping recalled to the Nandu reporter that until May 2020, she waited for the news that Weimingzan had not entered Zhejiang Medical Insurance, "I was more desperate, and I felt more guilty about my child's self-blame, because I felt that it was my parents who were incapable and did not have so much money to give her medicine." She thought, "If I have a lot of money and don't need to go into health insurance, more than $2 million a year is not much for some people." I'm annoyed. ”
At present, Weimingzan has not been included in the national medical insurance catalog. However, various places have explored the protection of drugs for rare diseases.
"Some regions have included mucopolysaccharidosis IVA in local medical insurance, such as Chengdu." Guo Jinchuan, director of information research of the Beijing Pain Challenge Public Welfare Foundation, introduced to Nandu reporters that for example, in 2021, the Chengdu Municipal Medical Security Bureau issued the "Scope and Identification Standards of Drugs for Rare Disease Drug Protection in Chengdu", and Weimingzan was included in it, enjoying rare disease drug protection funds, which were calculated cumulatively and reimbursed in segments within a treatment year.
Guo Jinchuan said that at present, inclusive commercial supplementary medical insurance in various places is the main way to protect such rare diseases. He explained that the reimbursement rules of inclusive insurance vary greatly from place to place, and the main role is to effectively supplement medical insurance reimbursement.
In Guangdong, inclusive commercial supplementary medical insurance in some cities already supports patients. Li Xiaoli, a parent of a Guangzhou patient, told the Nandu reporter that through "Sui Sui Kang", up to 1 million can be reimbursed every year.
In 2023, "Shenzhen Huimin Insurance" will include 7 self-paid drugs for rare diseases, including Weimingzan, into the insurance, stipulating that the annual cumulative amount of personal expenses of more than 16,000 yuan will be paid 50%, 60% and 70% respectively according to the time when the insured continuously participates in Shenzhen Supplementary Medical Insurance for Major and Extraordinarily Serious Diseases or "Shenzhen Huimin Insurance", with an annual payment limit of 500,000 yuan.
But for many rare disease families, under the high cost of drugs, universal insurance is very limited. Guo Jinchuan believes that it is difficult to rely on inclusive insurance alone to ensure that patients can continue to standardize their medication. In some places, the amount of inclusive insurance is not high, about 300,000 to 500,000, and there are pre-existing disease restrictions to reduce the reimbursement ratio.
Self-help for parents
Zhang Yuping thought that she could not wait any longer, there was no medical insurance, she decided to contact the pharmaceutical company herself to reduce the price.
In 2020, she tried to contact the Chinese staff of a pharmaceutical company, talking for hours, giving one reason after another, and striving for preferential use of drugs.
"I said that in such a large market as China, enterprises have come in through the fast approval channel, which shows the greatest care for patients with rare diseases." She recounted to the Nandu reporter the negotiation scene a few years ago, "If the drug effect is particularly good, I am willing to cooperate with the company to truly publicize the effect of the drug." She also confessed her and her husband's work to the other party, hoping to prove that she can give good care and guidance to her children, so that children can become adults, and can have a good impact on publicizing the efficacy of medicine.
"That time, I should have talked a lot, six or seven hours."
About a week later, she won the buy-one-get-one-get-one-free offer, but still had to pay more than 1 million out of pocket. Zhang Yuping struggled, not knowing if this was a way out to see the future, but at that time gritted his teeth or chose to use medicine, "The key is that I want my child to use medicine, if it has an effect, and strive to add chips for the next medical insurance." After several years of treatment, Zhang Yuping has now won a price of 500,000 yuan a year.
Zhang Yuping is not alone.
Many parents of patients take the initiative to contact pharmaceutical companies after learning of the diagnosis to obtain drug discounts for their children. They also tried to contact various resources such as gene therapy companies to consult on all methods such as going abroad for treatment, hoping to find a new way out.
In March 2022, Duanduan from Zhejiang began to play Weimingzan, which required 5 bottles a week, that is, 37,500 yuan. "I calculated the family's savings and decided that no matter how long I could use it, we would give it to him first." After weighing up, Luo Zhou quickly decided to give the child medicine, even if it was to be used for life, even if it might be a bottomless pit.
Under the high medical fees, Duanduan's father Luo Zhou also tried to contact the pharmaceutical company to communicate, "The prescription told me that 500,000 yuan a year at my own expense, and the rest of the medicine can be given away." "In the 58 weeks of treatment, the cost of medicine has cost more than 500,000 yuan.
In the hospital, Luo Zhou always stared at the hanging needle stuck into the end of the hand, adjusting the drip rate every 15 minutes, 3 ml and 6 ml per hour... 36 ml, slow to fast. Duan Duan no longer often cried because of the injection, and his quick adaptation made Luo Zhou only feel sad, "He used to resist it, every time I said that this is to lose energy, every time I lose, I am full of energy, you can go casually, run casually." ”
Zhengyu Mucopolysaccharide Rare Disease Care Center organizes these families with the same disease to help each other through the difficult times ahead. "There are very few patients with rare diseases, and many families are very confused and can't see what to do in the future. But if patients have a communication platform, they may have some comfort for each other psychologically. Zheng Qi introduced that at present, more than 600 patients have joined the care center, including less than 100 IVA patients.
Rare disease families participate in offline free clinic activities.
Patients' families have become volunteers at the care center, helping to organize offline free consultations, online forums and other activities, and more and more medical experts have come to the free clinics to diagnose and treat patients on the spot, share the latest treatment methods, local medical insurance and commercial insurance policies, etc.
Despair and hope
While drugs are about to be delisted, drug donations are also facing cancellation. In February this year, Luo Zhou applied for the last batch of donated drugs for Duanduan, which was only enough to last until the end of July.
"After the medicine is used up, if you buy it again, it will be the full price, about 1.9 million a year. If the weight of the end end rises next year, it will take 6 bottles of medicine, which is more than two million a year. "Luo Zhou calculated the accounts one by one, and could only come up with unbearable figures." Medicine is expensive, but for us, we can buy medicine in China, at least we still have options. If we really don't sell it, we really don't have any thoughts. ”
"I've envisioned the future many times." Luo Zhou was sober and desperate, "For me, I hope he can walk ahead of me, at least I can watch him go, right?" "He's my only child, and if I die later, what do you say he's going to do?" Who can take care of him? He just needs to live happily, and sometimes, that's all he can do as a parent. ”
When the "delisting" wind was released, Shin Shin, who had just been diagnosed, even had time to use medicine in the future.
Three months ago, Shin Shin, who was 3 and a half years old, was diagnosed with mucopolysaccharidosis. Father Xu Leyang sent many Xinxin photos to reporters: she was wearing a red princess dress with small sequins, holding a toy and smiling innocently, lying on the table to seriously answer questions from children's picture books, watching the children learn to dance through the glass.
Shin Shin wore a red princess dress with small sequins.
In the photo, she looks lively and happy, as if she has never experienced illness. But Xu Leyang knows that the older the child, the more obvious the symptoms will become.
"Since I was a child, I would fall on my head, and later I also found that her neck was a little short, her wrists were very loose and boring, and she had a little chicken breast." Xu Leyang told Nandu reporters that affected by rare diseases, the child underwent tonsil adenoid hypertrophy surgery at the beginning of the year, and was even found to be hearing loss.
In just a few months, Xu Leyang traveled all over the hospital, from knowing nothing about mucopolysaccharidosis to being half an expert. The child's treatment still costs a lot of money, and he and his wife can't leave their jobs, so they can only work overtime to earn money while visiting famous doctors. He didn't have time to think about the future, he only hoped that there would be a way to cure the child now.
In the face of the delisting of drugs, Zhang Yuping was very angry, "I will not give up the legal weapon to protect the interests of our children." She felt a kind of "abandonment", which is the only medicine, "We paid money and energy for it, and the company cannot just retreat, which is irresponsible to the patients." ”
After being angry and desperate, Zhang Yuping still hoped that the medicine would remain, but not to cure the disease, but to buy a waiting time for the child.
"Medical development also has an exploratory process, and perhaps there will be opportunities to break through the bottleneck." She has this expectation, "If I give my child the most effective treatment for the past 10 years, even if it is a little more costly, then after 10 years, she may wait for an opportunity so that she can take care of herself and shine." ”
Before hanging up the phone, Zhang Yuping confessed to the Nandu reporter, "I have checked a lot of information and have an objective understanding of this disease, that is, there is no cure." ”
Then she added, "But as a mother, I don't seem to have much choice." ”
(At the request of interviewees, Li Xiaoli, Tong Tong, Luo Zhou, Zhang Yuping, Xin Xin, and Xu Leyang are pseudonyms)
Produced by: Nandu Instant
Written by: Nandu reporter Ao Yinxue