When Gu Ruofei was four and half years old, teachers at her school in Shaanxi province reported that she had trouble jumping during her dance class.
As her motor skills deteriorated, doctors in the provincial capital of Xi'an suspected the toddler may be afflicted by a metabolic disorder that stunted her growth. Blood tests in Beijing confirmed in 2004 that Gu had mucopolysaccharidosis (MPS), a progressively debilitating disease caused by the absence of an enzyme. Undetectable at birth, symptoms typically show up at one or two years old, and patients rarely live beyond 20 years.
MPS is a rare condition. Its prevalence " depending on how symptoms are categorised, can afflict one in 200,000 births for Gu's Morquio syndrome, or one in 500,000 in the mildest form of Scheie syndrome.
Treatment, usually directed toward the symptom, is arduous and expensive, requiring specialist teams of paediatricians, orthopaedists, surgeons, audiologists or ophthalmologists all working together.
Gu Ruofei, age 13, attending the opening ceremony of an advocacy and support centre started by her mother in Beijing to raise awareness of rare diseases. Gu suffers from a form of mucopolysaccharidosis (MPS) manifested as Morquio syndrome, caused by the absence of an enzyme. Photo: SCMP/Handout alt=Gu Ruofei, age 13, attending the opening ceremony of an advocacy and support centre started by her mother in Beijing to raise awareness of rare diseases. Gu suffers from a form of mucopolysaccharidosis (MPS) manifested as Morquio syndrome, caused by the absence of an enzyme. Photo: SCMP/Handout
Luckily for Gu, she has a mother who just would not give up. Zhang Yu, a book-keeper, spent years visiting every hometown doctor in search of a treatment for her only daughter, before moving to Beijing with her husband for a job as a reporter to be closer to China's best medical resources. Gu stayed in Xi'an, where her grandfather carried the little girl on his back everyday between home and school.
"I have been to many hospitals in Beijing, large and small, where all the doctors said there was no cure, even overseas," Zhang said in a phone interview with South China Morning Post. "It was very despairing to see one's child's stop growing and suffering."
In 2010, Zhang learned that a drug approved by the US Food & Drug Administration was on trial in Taiwan, which could extend the life expectancy of MPS patients.
The drug, Vimizim made by California-based BioMarin Pharmaceutical, costs US$450,000 for a year of treatment, an exorbitant cost for most families, and an impossible sum for a medically uninsured, average-income household in China.
"We made multiple trips to Taiwan to try our luck, but failed to get on the drug company's clinical trial because of a lack of insurance coverage [in mainland China]," Zhang said. "That means we could not afford to keep paying for the prescription once the trial ended."
MPS was absent from the approved list of rare diseases for insurance reimbursement in mainland China, due to limited state health care funding and the lack of data on their prevalence. MPS comprises 40 distinct types of lysosomal diseases, with small patient numbers in each, which means actuaries cannot accurately assess the potential cost to the health system.
Treatments for most rare diseases cost anywhere between 100,000 yuan and up to 2 million yuan (US$290,000) a year, said Li Linkang, executive director of the China Alliance for Rare Diseases in Beijing.
"Most patients, after being diagnosed, have no access to drugs because they either do not exist, or if they exist overseas, they are not available in China," said Li, whose non-profit advocacy and support group is scheduled to release a research in October of the prevalence of such conditions in the country. "For those that have been approved to be sold, most likely they are extremely expensive."
Changes are afoot, after China's drug regulator last year released the country's first catalogue of rare diseases, covering 121 disorders out of 7,000 known afflictions.
For the first time, clinical trial data from overseas would be accepted for the purpose of approving new drugs for sale in mainland China.
"The catalogue is a significant turning point because it provides for the first time a framework for subsequent policies to support their treatment, including new drugs registration and state health insurance drugs reimbursement," said Rebecca Lin Rui, who leads venture capital investments in the health care sector as partner at Eight Roads Ventures in Shanghai. "Multinational pharmaceutical firms have stepped up effort to introduce their drugs to China, but in terms of drugs development, Chinese start-ups in this area are few and far between."
China's market for rare-disease drugs may grow 41.5 per cent between 2017 and 2021, outpacing the 13.5 per cent average growth in developed markets such as the US, according to forecasts by CIF Insights and Frost & Sullivan.
"The biggest barrier for treating rare diseases is the lack of investment, which needs policy support," said James Xue Qun, founder and chairman of Beijing-based CANbridge Pharmaceuticals, a developer of drugs for rare diseases. "Over the past 30-plus years, almost all nations in the developed world and many developing ones have come up with regulatory changes to allow companies to make normal economic returns and give patients access to treatment."
This has attracted investments, so that rare-disease treatment now makes up roughly 40 per cent of all new drugs approved in the US in recent years. Over half of the most successful US biotech firms have drug development programmes in rare diseases, said Xue, a former China general manager of Genzyme before it was bought by Sanofi in 2011.
As the cost of DNA sequencing became cheaper over the past two decades, the genetic mutations that cause rare diseases can be better understood on the molecular level, Xue said.
"Rare diseases can now be addressed with emerging tools like gene therapy or cell therapy so that the drug research and development process is more efficient," he said. "This results in a higher chance of success, shorter development cycle and lower development cost."
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CANbridge has the license to market a drug from South Korea's GC Pharma for treating MPS Type II, also known as Hunter Syndrome, a debilitating disorder that afflicts almost exclusively male children, affecting two in 100,000 births.
The company, which is considering a stock market listing after raising US$113 million from several rounds of private-capital funding, plans to submit an application this year to market the drug.
Another company in this field is Beijing Continent Pharmaceuticals, which develops treatment for idiopathic pulmonary fibrosis (IPF), a rare disease where the lungs progressively and irreversibly deteriorates, giving the patient two to three years' lifespan from the time of diagnosis.
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Continent has commercialised an IPF drug in 2011 through its own research and cooperation with its Japanese parent GNI Group. The Beijing company is also conducting clinical trials on connective tissue disease associated interstitial lung disease and radiation-induced lung injury.
Aptorum Group, a Hong Kong start-up, is using big data analytics to cut research cost and shorten the time needed to develop drugs for rare diseases. The company is seeking to repurpose approved drugs for new treatments, such as rare cancers, said its head of research and development Thomas Lee.
He estimated that by using analytics tools, it could cost as little as US$2 million to US$3 million to identify a potential repurposed drug candidate, relatively affordable to the Nasdaq-listed two-year-old firm.
Zhang Yu's personal search for her daughter's cure has evolved into a quest for China's broader society to better understand rare diseases.
She set up the China MPS Rare Disease Care Centre in Beijing in 2012, a non-profit support group for sick infants and their families, which also raises awareness for the rare condition.
Only 13 of the drugs used for the 121 diseases on the Chinese catalogue of rare diseases qualify for reimbursement under China's national health insurance. BioMarin's elosulfase alfa, with the trade name Vimizim used for treating Gu's Morquio type A syndrome, is still off that list.
When the drug was launched in the US in 2014, Zhang arranged for financial help to send her daughter to America for treatment.
Gu, who is now 20, is studying fine arts in Maryland to become a graphic designer, where she aims to put her artistic talent to good use. Her treatment course cannot reverse the years of damage inflicted by MPS, but has halted the deterioration in her condition, and helped her regain enough body strength to let her pursue higher education.
"We had our moments of feeling completely hopeless, but with sheer determination and faith we managed to see some light at the end of the tunnel," Zhang said. "That is the message I want to share with others."
This article originally appeared in the South China Morning Post (SCMP), the most authoritative voice reporting on China and Asia for more than a century. For more SCMP stories, please explore the SCMP app or visit the SCMP's Facebook and Twitter pages. Copyright © 2019 South China Morning Post Publishers Ltd. All rights reserved.
Copyright (c) 2019. South China Morning Post Publishers Ltd. All rights reserved.