Recently, it has been reported that Nitisinone, a specialized drug for treating the ultra-rare disease Tyrosinemia Type I, has encountered a supply shortage in the Chinese market two years after being included in the national medical insurance. At least eight children (the youngest being just six months old) are facing the risk of treatment interruption.
The shortage stems from the discontinuation of production by an overseas generic drug manufacturer. Nitisinone was listed as the top priority in the "First Batch of Encouraged Generic Drug Catalog" by China’s National Health Commission in 2019, but no domestic generic version has been approved for market release to date.
Industry experts specializing in rare diseases note that while the number of affected children may be minimal, this case exemplifies the broader challenges in rare disease drug supply. Due to the small patient population, drug sales revenue often fails to cover production costs, leaving little incentive for generic manufacturers to produce these drugs even years after patent expiration. The shortage reflects not only difficulties in original drug innovation but also imbalances between corporate interests, market mechanisms, and public policies.
**"Policy in Place, but Drugs Unavailable"** Parents of affected children, such as Mr. Li from Shanghai, revealed that families were informed by Guangzhou Hanguang Pharmaceutical, the drug’s distributor, that existing domestic stock could only provide two bottles per patient, with no additional supply planned.
Tyrosinemia Type I is a genetic metabolic disorder requiring lifelong Nitisinone treatment to prevent toxin accumulation, which can lead to liver cirrhosis or cancer. While liver transplantation is an alternative, it is typically reserved for cases where drug therapy fails or liver cancer is suspected. Some families, facing drug shortages, have reluctantly opted for transplants.
Dr. Han Lianshu, a pediatric endocrinologist at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, explained that Tyrosinemia Type I is extremely rare, with an incidence of about 1 in 50,000–60,000 in China. Nitisinone, the only globally approved treatment, works by inhibiting 4-hydroxyphenylpyruvate dioxygenase and must be paired with a specialized diet low in tyrosine and phenylalanine.
**Supply Chain Breakdown** Mr. Li noted that after Nitisinone’s inclusion in insurance, dual-channel pharmacies became a key procurement route. However, the supply disruption—attributed by the manufacturer to unmet sales expectations and FDA non-certification of raw materials—has left families stranded. Guangzhou Hanguang Pharmaceutical confirmed the halt in production by its Canadian supplier.
Currently, eight Nitisinone products, all imported, are registered in China. While Swedish Orphan Biovitrum (Sobi), the original developer, obtained approval for its version, the company stated it has no immediate plans to enter the Chinese market.
**Potential Solutions and Challenges** With no domestic generics available, families are exploring alternatives such as overseas purchases or temporary import programs for clinically urgent drugs. However, these options come with high costs—ranging from ¥7,000–¥8,000 per bottle for Turkish generics to ¥33,000–¥35,000 for Swedish originals—far exceeding insured prices (¥4,488/bottle, with 30–50% reimbursement).
A temporary import mechanism, introduced in 2022, allows designated hospitals to apply for urgent rare disease drug imports. Yet, such imports are ineligible for insurance coverage, and logistical hurdles remain due to scattered patient demand nationwide.
For now, some families are resorting to dose reduction—a risky measure that may necessitate liver transplants if toxicity escalates. As Mr. Li shared, his child’s medication has already been rationed, underscoring the urgent need for sustainable solutions.
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