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Hebei Daily | “Orphan Drugs” — Not Alone

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发布时间：2025-04-10

【概要描述】 Stiripentol dry suspension is an “orphan drug” exclusively manufactured in China, developed by Shijiazhuang Sihua Pharmaceutical Group, and indicated for the treatment of refractory epilepsy in children. In the first quarter of this year, this orphan drug was introduced into more than 100 Grade-II-A or higher medical institutions in Beijing, Shanghai, Zhejiang, and other regions, achieving strong sales performance.

Hebei Daily | “Orphan Drugs” — Not Alone

Sitiguan Alcohol Dry Suspension is an “orphan drug” developed by Shijiazhuang Sihua Pharmaceutical Group and exclusively manufactured in China, indicated for the treatment of refractory epilepsy in children. In the first quarter of this year, this orphan drug was introduced into more than 100 Grade-II-A and above medical institutions in Beijing, Shanghai, Zhejiang, and other regions, achieving strong sales performance.

“Orphan drugs” refer to medications used to prevent, treat, or diagnose rare or ultra-rare diseases. Pediatric drugs for rare diseases are often dubbed the “orphans” among orphan drugs. How has Shisi Pharmaceutical achieved breakthroughs in this field? A reporter conducted an interview to find out.

■ Developing “orphan drugs” can both meet the medication needs of pediatric patients in China and enhance competitiveness in the pharmaceutical market.

On April 2, at the Pharmaceutical Research Institute of Shijiazhuang No.4 Pharmaceutical Group, Sun Lijie, Executive President and General Manager of the R&D Center, expressed great satisfaction upon hearing the sales team’s briefing on the market demand for sitagliptin dry suspension.

“Starting this January, stiripentol has been officially included in the national medical insurance scheme, providing greater assurance of access to the medication for patients,” said Sun Lijie. He added that it took a full decade from the initiation of research and development to the drug’s market launch, and that this “orphan drug”—used to treat severe myoclonic epilepsy in infants (Dravet syndrome)—is now fulfilling its unique therapeutic role.

Dravet syndrome is a rare, refractory epileptic syndrome in children. As a prototypical form of intractable epilepsy, it is classified by the International League Against Epilepsy as one of the most disabling epilepsies. Dravet syndrome can lead to severe epileptic encephalopathy and is characterized by early age of onset, high seizure frequency, significant cognitive impairment, and a high mortality rate.

Dravet syndrome has been included in China’s First Batch of Rare Diseases Catalogue. Relevant data indicate that the overall incidence of Dravet syndrome is approximately 1 in 20,000 to 40,000, accounting for about 29.5% of all forms of myoclonic epilepsy in children and 7% of epilepsies in infants and young children under the age of three, making it a relatively common rare disease.

Given China’s large population base, the number of individuals affected by rare diseases is substantial when calculated as a proportion of the total population. Sun Lijie stated that this presents both an opportunity and a significant responsibility for businesses.

Stiripentol is one of the most effective drugs for treating Dravet syndrome and is regarded as the last line of defense in its management. In 2001, stiripentol was designated an “orphan drug” by the European Union. However, since the originator formulation of stiripentol has not been approved for marketing in China, pediatric patients in the country have for a long time either had no access to the medication at all or have had to go to great lengths to obtain expensive imported formulations.

For relatively common diseases, rare diseases affect a small patient population, have low market demand, and entail high R&D costs, which typically deter pharmaceutical companies from allocating resources to their development and production. In recent years, Shisi Pharmaceutical has taken a coordinated approach to advancing the research and development of innovative drugs, generic drugs, specialty APIs, and products undergoing bioequivalence evaluation, with a particular focus on developing pediatric- and geriatric-friendly formulations. When selecting R&D targets, Sun Lijie set his sights on sitagliptin.

On the one hand, pediatric patients in China face an almost complete lack of available medications; on the other hand, foreign pharmaceutical companies are reluctant to invest substantial human and financial resources in developing the Chinese market. The development of sitagliptin not only addresses the unmet medication needs of domestic pediatric patients but also positions the product to be highly competitive in the pharmaceutical market.

Stiripentol is available in two dosage forms: capsules and dry suspension. The dry suspension is a formulation that is well-suited to children’s physiological characteristics. Shisi Pharmaceutical has exclusively submitted a marketing application for the stiripentol dry suspension within China and, on the grounds of “a new variety, dosage form, and specification of pediatric medicinal products that are consistent with children’s physiological characteristics,” it has been included on the priority review list.

■ Break through technical bottlenecks and innovate in areas such as synthetic process routes and drug preparation methods.

In recent years, Shisi Pharmaceutical has been primarily focused on the production of large-volume parenterals, giving the impression that this single product line once dominated the company’s operations. In response to the broader trend of industrial upgrading, Shisi Pharmaceutical has continuously deepened the integrated collaboration among industry, academia, research institutions, and end-users, achieving numerous innovative breakthroughs in recent years in areas such as innovative drugs, high-end generic drugs, and specialty APIs. Stiripentol is one such innovative achievement.

“Producing a high-quality generic drug also hinges on innovation,” said Sun Lijie. With regard to Dravet syndrome, developing a medication that is well-suited to the genetic heritage and physical characteristics of the Chinese population requires breaking through technical bottlenecks and overcoming patent barriers associated with the original innovator’s synthesis methods—specifically, by driving technological innovation in areas such as synthetic process routes and drug formulation techniques.

In the current pharmaceutical industry, integrated development of active pharmaceutical ingredients (APIs) and finished dosage forms has become a prevailing trend. Mastering both API and formulation manufacturing technologies helps ensure consistent drug quality and control costs.

Lv Jinwei, head of the Second Department of the API Research Center at Shisi Pharmaceutical, together with the R&D team, has successfully developed the active pharmaceutical ingredient stithiol. “We have invested nearly RMB 2 million just in the reference formulation,” said Lv Jinwei. He emphasized that APIs are the active ingredients in pharmaceutical products, and that developing and manufacturing specialty and patented APIs requires substantial capital investment and robust R&D capabilities.

Considerable effort was expended by the R&D team to synthesize stigmasterol with higher purity.

According to Lu Jinwei, the stigmasterol compound exists as cis–trans isomers, with the trans isomer being the pharmacologically active form and the cis isomer exhibiting virtually no activity. Through repeated experimentation, the research team innovatively employed a retrosynthetic approach, conducting multiple chemical reactions to generate cis-stigmasterol intermediate impurities. This synthetic method has been granted an invention patent, enabling the production of high-purity, high-quality cis-stigmasterol intermediate impurities that can be directly used as superior reference standards for monitoring impurity levels in stigmasterol intermediates or finished stigmasterol products.

Innovation ensures the efficacy and safety of pharmaceutical products. In the production of sitagliptin API and formulations, Shisi Pharmaceutical has obtained a total of four invention patents covering API development, analytical testing, and formulation technologies.

At Workshop 209 of Shisi Pharmaceutical, pharmaceutical products are steadily moving along a fully automated, interconnected production line consisting of 12 carton-packaging stations. According to the workshop manager, Workshop 209 is equipped entirely with automated and intelligent manufacturing equipment, enabling fully enclosed, automated handling and transportation of raw materials. This not only significantly boosts production efficiency but also further safeguards the overall quality of the products.

By the time the interview concluded, it was already after working hours, yet the R&D staff in the Drug Research Institute’s laboratory were still diligently conducting experiments and analyzing data.

Currently, Shisi Pharmaceutical has more than 200 new products in development, spanning areas such as oncology, antiviral therapy, cardiovascular health, gastroenterology, and anesthesia, marking a shift in its drug R&D from generic replication toward original innovation. “Shisi Pharmaceutical employs over 500 R&D professionals, the majority of whom are young people around the age of 30. We are confident that, through our own efforts, we will develop more ‘Made-in-China’ medicines that meet market needs and public expectations,” said Sun Lijie. He added that technological innovation and social responsibility have enabled Shisi Pharmaceutical to successfully break down technical barriers, providing accessible and affordable treatment options for patients with rare diseases and ensuring that “orphan drugs” are no longer isolated or neglected.

(Originally published in Hebei Daily)

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