A mother of a rare disease patient has been pursued abroad, and the only drug will be delisted from the domestic market for polysaccharides | storage | disease patients

"I must make some efforts to make them have medicine available." In June 2023, Zheng Yu boarded a plane to the United States.

In addition to visiting her daughter, she also has an important task on this trip - to strive for a face-to-face communication with the head of the headquarters of Baiao Wanli Pharmaceutical, the manufacturer of the special drug "Weimingzan".

"Weiming Zan" is currently the only drug in the world that treats mucopolysaccharide storage syndrome type IVA, and Zheng Yu's daughter suffers from this rare disease. In 2016, before the drug entered China, Zheng Yu sold his house and tried every means to send his daughter to the United States for treatment.

In May 2019, "Weiming Zan" was approved for listing in China. Its emergence brings hope to patients, and the annual expenditure of millions of yuan purely out of pocket has also deterred many people.

Nowadays, this "expensive hope" seems to be gradually fading away.

According to China Youth Daily, drug manufacturer Baiao Wanli Pharmaceutical has announced that it will no longer renew the import drug registration certificate of "Weimingzan" in China, which will expire in May 2024.

This means that starting from June next year, IVA patients with mucopolysaccharide storage syndrome in China may face a situation where there is no available medication.

As the mother of a rare disease patient and the founder of a mucopolysaccharide rare disease care center in China, Zheng Yu has always been unwilling. "I want to feedback the needs of domestic patients to pharmaceutical companies, hoping that they can continue to provide drug protection. This is not only for my daughter, but also for this group of rare disease patients in China."

The only effective medicine

Mucopolysaccharide storage syndrome is a disease caused by a mutation in the hydrolytic enzyme that degrades mucopolysaccharides in human cells, resulting in the loss of their activity and the inability of mucopolysaccharides to be degraded and metabolized, ultimately leading to their accumulation in the body. On May 11, 2018, the National Health Commission and five other departments jointly formulated the "First Batch of Rare Disease Catalogue", which included mucopolysaccharide storage syndrome.

Data shows that this disease is a very important type of lysosomal storage disease, which can be divided into 7 types: type I, II, III, IV, VI, VII, IX, among which type IV is divided into IVA type and IVB subtype. Although the pathogenic genes and clinical manifestations of each type vary, due to the accumulation of mucopolysaccharides as the substrate, it is collectively referred to as mucopolysaccharide storage disease.

Recently, Qiu Wenjuan, the chief physician of the Department of Pediatric Endocrinology and Genetics at Xinhua Hospital affiliated with Shanghai Jiao Tong University, stated in an interview with The Paper that mucopolysaccharide storage syndrome is most commonly type II, followed by type IV. Type IVA is a disease caused by the lack of activity of enzymes involved in glycosaminoglycan metabolism.

She introduced that MPS IVA type children generally have no abnormal manifestations at birth, but as they age, they gradually develop into severe skeletal and joint abnormalities and a series of other organ injuries, leading to short stature, skeletal deformities, respiratory diseases, spinal cord compression, heart disease, visual and auditory damage, tooth deformities, etc. Patients with MPS type IVA typically have more extensive and severe bone injuries than other types of MPS.

"Most of these patients are children, some as young as a few years old, and some as late as 10 years old. Their intelligence is normal, and many patients are diagnosed at a young age. However, by the age of 20, they may experience difficulty walking and spinal cord compression. Respiratory failure is the main cause of death for patients, and they may need to rely on ventilators in the later stage. Many patients may not live to be 30 years old," said Qiu Wenjuan.

At the hospital where Qiu Wenjuan is located, a total of hundreds of patients with mucopolysaccharide storage syndrome have been treated, most of whom are children. Among them, about 20% -30% of patients are type IV. In recent years, only one patient has been treated with "Weimingzan".

Weimingzan is produced and developed by Baiao Wanli Pharmaceutical Company, headquartered in California, USA. This drug was approved for sale in the United States in February 2014 and can significantly improve muscle strength, joint function, cardiovascular function, and quality of life for patients.

In November 2018, China released the first batch of "Clinical Urgent Overseas New Drug List", in which "Weimingzan" was included. It is currently the only drug in the world to treat mucopolysaccharide storage syndrome type IVA.

"This medication requires intravenous infusion once a week, and the dosage and treatment cost vary depending on the patient's weight. For example, for a patient weighing 10 kilograms, the weekly treatment cost is about 30000 yuan." Qiu Wenjuan admitted that if solely relying on self payment, the annual cost of using this medication would exceed one million yuan, and few patients could afford such high costs, and many families would give up treatment as a result.

She also revealed that there was a child in the hospital who received regular infusion of "Weimingzan" and had been treated for a year, with significant therapeutic effects. The family received a complimentary medication while purchasing their own medication, and in addition to local medical insurance, they self funded nearly 200000 yuan per year. Currently, the child's walking distance has significantly improved, their strength has recovered, and their condition has not worsened.

There are currently no other recommended treatment options besides this medication. "Currently, there are also some patients' families attempting hematopoietic stem cell therapy in China, but according to international guidelines and the" Rare Disease Diagnosis and Treatment Guidelines, "considering the risk of hematopoietic stem cells and the less prominent central nervous system symptoms in patients with mucopolysaccharide storage syndrome type IVA, hematopoietic stem cell therapy is not recommended as a treatment for this type of patient," said Qiu Wenjuan.

The Road of Seeking Medical Treatment for Rare Disease Families

Zheng Yu's daughter is an IVA type patient with mucopolysaccharide storage syndrome, diagnosed in 2004 when she was only 4 and a half years old.

"When our daughter was born, we didn't know she had this disease, her development was normal, and she wasn't short, but at around the age of 4, we found that her spine was a bit kyphosis," Zheng Yu said. He went to see many doctors at the time but couldn't find any problems. Later, one time when her daughter was dancing, other parents reminded her that her child's legs couldn't lift up, and she realized the seriousness of the problem.

Zheng Yu took his daughter to a children's hospital in Shaanxi. The orthopedic doctor suggested taking a full body X-ray examination. After another expert consultation, it was suspected that he had mucopolysaccharide storage syndrome.

"At that time, the doctor told me that this was a rare disease. He had been in the industry for 20 years and had only seen two such patients, one of whom was my daughter." This was also the first time Zheng Yu had heard of mucopolysaccharide storage syndrome.

That year, she took her daughter to Peking Union Medical College Hospital and was diagnosed with mucopolysaccharide storage syndrome type IVA. However, doctors were unable to come up with a better treatment plan.

In order to treat his child, Zheng Yu visited many hospitals in Beijing, Shanghai, and Guangzhou. If Western medicine was not effective, he would seek treatment from traditional Chinese medicine. She learned that hematopoietic stem cell transplantation is also being developed as a treatment method in China, but was informed that the risk is high and it is not currently the recommended treatment method internationally.

Zheng Yu compared his daughter's disease progression to "boiling a frog in warm water.".

"The child's bones are being depleted day by day, and she is no longer growing at a height of 1 meter. Being short is still one aspect, and her biggest concern is cervical compression. She is afraid that one day she will be paralyzed and can only lie on the bed. Such worries make Zheng Yu's whole family live in fear every day," I don't know when this will happen in the future. "

From the age of 4 and a half to 9, Zheng Yu spent a lot of time searching for effective treatment methods for his daughter. She once inquired about a specific drug in the United States that is currently under development and undergoing clinical trials in multiple regions around the world. She even pursued drugs and flew to Australia to attend international conferences to learn about the latest research progress in drug therapy.

In 2009, she established contact with the mucopolysaccharide association in Taiwan, China, China, through friends' introduction, and got to know more families of mucopolysaccharide patients. Seeing that they organized activities for patients and fought for their rights, Zheng Lei felt motivated to move forward.

"A person's strength is too small, perhaps establishing a patient organization would have a greater strength." In 2012, Zheng Yu led the establishment of the Beijing Zhengyu Adhesive Polysaccharide Rare Disease Care Center.

She contacted the Asia Pacific regional leader of Baiao Wanli Pharmaceutical Company and established contacts with relevant research institutions. She also held charity events to help patients overcome the haze and timely reported patient conditions to pharmaceutical companies. At the same time, she also fought for international medication opportunities in this rare disease group.

In February 2014, "Weimingzan" was approved for sale in the United States and can be used to treat IVA patients with mucopolysaccharide storage syndrome. After this news was released, Zheng Yu wanted to try to get his daughter to use this medicine.

In 2016, Zheng Yu sold his house and, with the help of friends, sent his daughter to the United States for treatment, accompanied by his grandparents.

Afterwards, Zheng Yu found the relevant person in charge of Baiao Wanli Pharmaceutical Company in the United States, inquiring whether treatment costs could be covered through medical insurance. With the help of the pharmaceutical company, he applied for insurance six months later, with a cost of about $8000 per year, which can basically cover 80% of drug treatment costs. After more than two years, his daughter completed local high school courses and was admitted to a local university, and can cover drug treatment through student medical insurance at a cost of over $1900 per year.

Zheng Yu said that due to taking medication too late, her daughter's hip bone has deformed, affecting her walking. Currently, she mainly relies on a wheelchair for transportation, but can stand for a moment and have the ability to live independently and cook independently.

But she still appreciates the pharmaceutical company, which has provided great help in applying for insurance, "allowing my daughter to receive treatment there with peace of mind and her condition under control."

Heard about the efforts made after delisting

In 2018, "Weimingzan" applied for listing in Chinese Mainland. By virtue of the green channel opened by the Chinese government for rare disease drugs, this drug was officially approved for listing by the State Drug Administration in May 2019.

At the care center created by Zheng Yu, there are approximately 100 IVA patients with mucopolysaccharide storage syndrome, and 13 patients are currently using this drug for treatment, including those from Zhejiang, Jiangsu, Anhui, Hunan, and other regions.

According to the China Youth Daily, as a high-value drug, "Weimingzan" appeared on the pre selection list of medical insurance negotiations in 2021, but the negotiations ultimately failed. It did not participate in medical insurance negotiations in 2022 and is currently not included in the national medical insurance directory. It is only included in some local medical insurance and welfare insurance.

Shanghai Huibao has included "Weiming Zan" in the drug catalog.

In 2021, Jiangsu included mucopolysaccharide storage syndrome type IVA in the first batch of rare disease drug protection targets in the province, with a medical insurance payment ratio ranging from 80% to 90%, of which 90% were paid above 700000 yuan; Shanghai's urban customized commercial supplementary medical insurance "Huhuibao" has also been included in "Weimingzan", with a maximum insurance amount of up to 1 million yuan. Among them, the payment ratios for non history patients and history patients are 70% and 30%, respectively.

Zheng Yu stated that among the 13 patients at her care center, none of them fully paid for their medication at their own expense. They mostly relied on the "buy medicine get medicine" strategy of pharmaceutical companies, combined with local commercial insurance such as "benefit the people". On this basis, each family also had to pay an additional nearly 200000 yuan per year.

However, the good times did not last long. Starting from the end of 2022, Zheng Yu gradually learned from patients and the marketing department of pharmaceutical companies that the company is unable to continue assisting patients with "drug giveaways" in China.

Just recently, Baiao Wanli Pharmaceutical Company also told China Youth Daily that it will no longer renew the import drug registration certificate of Weimingzan in China. The registration certificate will expire in May 2024.

In response to the aforementioned media, the pharmaceutical company stated, "The complex market access rules make the supply of drugs unsustainable, especially in the treatment of rare diseases. Despite our best efforts in the past few years, we have not been able to encourage Weimingzan to enter the medical insurance reimbursement system. We have decided not to renew the import drug registration certificate for this product."

Upon hearing the news of the drug being delisted in China, Zheng Yu's first reaction was, "Did the pharmaceutical company keep patients out of the market?"

Zheng Yu tried to communicate with a pharmaceutical company, but now the person in charge of the Asia Pacific region of the company is no longer answering her phone calls or responding to any messages from her.

This prompted her to make up her mind to directly go to the headquarters of pharmaceutical companies in the United States and communicate with them about the follow-up medication issues of domestic patients, "For my daughter, and also for these rare disease patients."

Zheng Yu bluntly stated that as the head of a patient organization and also a patient's parent, he should step forward and do his best to ensure the survival of patients. "Pharmaceutical companies cannot ignore patients for economic benefits. After discontinuing medication, how should these patients in China be treated? Where should they buy this medication? Moreover, it is still a medication that requires intravenous injection and cannot be directly purchased orally. Pharmaceutical companies cannot do this, they come and go."

Zheng Yu said that parents of patients had also consulted before, hoping to receive treatment from Weimingzan in the United States like her daughter. "Due to the complexity of insurance in the United States, which changes every year, it is difficult to apply for the insurance I purchased for my daughter now. At the same time, the person in charge of the pharmaceutical company who helped apply for this insurance has resigned, and it will be difficult later on. When the child goes to the United States for treatment, the whole family will face many difficulties. If the child is too young and the couple will have to live separately for a long time, there will be many difficulties."

In the families of patients Zheng Yu knows, only 1-2 patients have chosen to receive treatment in the United States for many years, and some have attempted to immigrate to Australia for treatment, but there are also many parents who have given up treatment.

She often thinks about her daughter's future, "This medication needs to be used for a long time. Perhaps one day, she will graduate and return to China. If there is no medicine available in China, what should she do?"

Zheng Yu hopes that one day, no matter where rare disease patients are, there will be medicine available.

In her opinion, currently, the rare disease population in China is receiving increasing attention and assistance from the government and various sectors of society. Previously, high-value drugs approved for the treatment of spinal muscular atrophy in China have been included in medical insurance, such as the once sky high priced drug Noxinasone Sodium, which costs 700000 yuan per injection, and the Lishipulan Oral Solution Dispersible Powder, which was priced at over 60000 yuan per bottle when it was launched. These drugs have greatly reduced the burden on patients after entering medical insurance, and also made Zheng Yu feel a glimmer of hope.

Now she looks forward to one day, with the joint support of the country, pharmaceutical companies, and various sectors of society, ensuring the medication of existing MPS IVA patients, and also hopes that more drugs or other treatment methods will appear to solve the current treatment difficulties.