21st Century Business Herald reporter Zhu Ping Intern Li Jiaying Beijing report Recently, the State Food and Drug Administration decided to suspend the import, sale and use of the anti-epileptic drug levetiracetam concentrated solution for injection under the multinational pharmaceutical company UCB Pharma S.A., and investigate and deal with related issues in accordance with the law. The drug supervision and administration departments of each import port shall suspend the issuance of import clearance certificates for the product.
This event then triggers a chain reaction. USBI injection was cancelled from the Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance region drug collection and procurement qualifications. On September 1, the Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance Procurement Working Group announced the determination of substitute enterprises such as Puli Pharmaceutical and Jichuan Pharmaceutical to supply Shanghai and Zhejiang Province respectively.
For the treatment of the State Food and Drug Administration, a Yosebive statement obtained by the 21st Century Business Herald reporter said that the suspension of imports of its concentrated solution for levetiracetam injection was caused by an error in the validity period label. In a recent off-site inspection of the drug overseas, the State Food and Drug Administration found that the validity period of some batches of the drug was inconsistent with the validity period of the registration approval.
Since it was approved for listing in 2017, USBE's concentrated solution for levetiracetam injection has been in the Chinese market for 5 years and has occupied a large market share for a long time. According to the PDB database sample hospital data, in 2021, the sales of anti-epileptic drugs in the sample hospitals will be 1.498 billion yuan, and the amount of drugs purchased by public hospitals nationwide will be about 5.003 billion yuan. In 2021, the hospital sales of the concentrated solution sample for levetiracetam injection were 31.78 million yuan, accounting for 2.1% of the 1.498 billion sales of epilepsy drugs in the entire sample hospital. However, with the continuous entry of local pharmaceutical companies, the market competition is very fierce, and more than 10 pharmaceutical companies have been approved for generic drugs. Especially after this incident, will it trigger a greater "domino" effect? Will its market dominance be further weakened? How will Unisby respond to the follow-up?
The selection of the collection was cancelled
On August 22, the Website of the State Food and Drug Administration published an announcement on the suspension of the import, sale and use of the Belgian pharmaceutical company URS bileracetam concentrated solution for injection. The NmPA made this decision based on the results of a recent off-site inspection of a drug abroad. The inspection found that the validity period of some batches of levetiracetam injection concentrated solution (import registration certificate number: H20170341, specification 5ml: 500mg, trade name Kaipulan) was inconsistent with the validity period of the registration approval. According to the State Food and Drug Administration, the latest issuance date of the concentrated solution of DEXTIracetam for injection is April 20, 2022, and the expiration date is April 19, 2027.
Levetiracetam is a well-known antiepileptic drug that was first marketed in the United States in tablet form in 1999. In 2006, levoethylracetam was listed in China under the trade name Caburan. From the perspective of dosage forms, levetiracetam not only has a concentrated solution for injection, but also an oral dosage form such as tablets and oral solutions. The concentrated solution for levetiracetam injection is suitable for the treatment of partial seizures (with or without secondary generalized seizures) in adults and children with epilepsy in children over 4 years of age, and can be used as an alternative to administration when the patient is temporarily unable to apply oral preparations.
In order to ensure the safety of public drug use, in accordance with the relevant provisions of the Drug Administration Law of the People's Republic of China, the State Food and Drug Administration decided to suspend the import, sale and use of the concentrated solution for injection of USPIracetam in China from August 22, and investigate and deal with related issues according to law. The drug supervision and administration departments of each import port shall suspend the issuance of import clearance certificates for the product.
On the same day, Unispec said the incident was caused by a valid identification error on the packaging of four specific batches of levetiracetam concentrated solution products for injection. USBI carried out the investigation as soon as it received the inspection results, and completed the voluntary recall of the batch involved, and is now actively cooperating with the regulatory authorities to work closely with the overseas factories involved in the incident to take targeted rectification measures with a view to restoring the supply of the drug in the Chinese market as soon as possible. In addition, Unisby also said that the four specific batches of the concentrated solution for levetiracetam injection involved in this incident were all within the validity period of China's registration and approval as of August 24 this year.
This event quickly caused a market reaction. On August 24, the Shandong Provincial Public Resources Trading Platform announced the suspension of trading in the declared product of Shanghai Pharmaceutical Cardinal (Shanghai) Pharmaceutical Co., Ltd., levetiracetam concentrated solution for injection. At the same time, as the winning product of the collection, the bidding qualification of the concentrated solution for levetiracetam injection was cancelled. On August 29, the Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance Procurement Working Group announced the cancellation of the qualification for the drug collection and procurement in the Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance region of the Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance region for the concentrated solution of Youshibi Pharmaceutical Levaceracetam for injection. The substitution process will be based on the relevant provisions of the "Yangtze River Delta (Shanghai-Zhejiang-Anhui) Alliance Regional Centralized Drug Procurement Document (CSJ-YD2022-1)", and other qualified alternative enterprises will supply the provinces selected by USE than the original selection, including Zhejiang and Shanghai.
In addition, the concentrated solution for levetiracetam injection is also the third batch of drug varieties. The drug was the first dosage form included in the national collection at that time, so the procurement cycle set by the Medical Insurance Bureau was 1 year, and after 1 year, it was renewed by each region according to the implementation of the contract. The highest effective declared price of levetiracetam injection in this collection is 340 yuan per bottle, and the price of Unispec is 85 yuan per bottle, ranking third, with a decrease of 75%. The supply area selected by Unisby is Beijing, Tianjin, Hunan, Shanghai, Heilongjiang, Guizhou and Shaanxi, and the renewal of bids is completed in some provinces and cities after the expiration of the first year of procurement.
In addition to USBY, Chongqing Shenghuaxi Pharmaceutical, Hainan Puli Pharmaceutical and Hebei Renhe Yikang Pharmaceutical won the bid. Among these three companies, there will also be substitute suppliers for Unispec. According to the "National Centralized Procurement Document for Drugs (GY-YD2019-2)", when the selected enterprises during the procurement cycle are unable to supply, etc., so that the agreement cannot continue to be performed, the replacement supplier enterprises are determined from other selected enterprises of the same variety.
The market is changing
In China, epilepsy has become the second most common disease in neurological science after headache, and the World Health Organization (WHO) has also listed epilepsy as one of the five neurological and psychiatric diseases in the global focus on prevention and treatment. According to the WHO, there are about 50 million people with epilepsy worldwide, of which 40 million are in developing countries. In China, there are about 10 million people with epilepsy, of which 6 million still have seizures every year. The domestic anti-epileptic drug market has broad prospects, and the overall market size exceeds 5 billion. According to the PDB database sample hospital data, in 2021, the sales of anti-epileptic drugs in the sample hospitals will be 1.498 billion yuan, and the amount of drugs purchased by public hospitals nationwide will be about 5.003 billion yuan.
The domestic anti-epileptic drug market is highly concentrated. According to the "2021-2025 Global Anti-Epileptic Drug Industry In-depth Market Research and Key Regional Research Report" released by the New Thinking Industry Research Center, the top five anti-epileptic drug types on the market are sodium valproate, levetiracetam, oxcarbazepine, pregabalin and lamotrigine, and the total market share of these five drugs has reached more than 85%. In the case of high market concentration, levetiracetam can still firmly grasp the top three positions.
PDB data shows that in the first quarter of 2022, the sales of levetiracetam in the sample hospital exceeded 76 million yuan, accounting for 20.19% of the sales of anti-epileptic drugs. Among them, the total sales amount of concentrated solution for levetiracetam injection is about 13.27 million yuan, accounting for 17.4% of the total sales of levetiracetam.
It has been 5 years since USBE's concentrated solution for levetiracetam injection has been in the Chinese market. In July 2017, the drug was approved for marketing in China. Previously, the drug was approved for marketing in the European Union and the United States in March and August 2006, respectively. For 5 years, Levetiracetam has provided Unisby with good revenue growth in the Chinese market. According to the financial report, in terms of net sales by region, YOSA's net sales in Europe and the United States in the first half of 2022 amounted to 2.255 billion euros, while the international market outside this reported net sales of 506 million euros. Among them, China became the second largest market in this part with 90 million euros, an increase of 50% year-on-year. During the reporting period, levetiracetam contributed net sales of €380 million to UNSBY, a decrease of 21.65% year-on-year and 14% of anti-epileptic and immune drugs.
With the suspension of imports, sales and use, the proportion of the concentrated solution for injection of USSbi levetiracetam in the domestic market may decline. The opportunity for local companies to replace them may already be here.
At present, a number of generic drugs related to pharmaceutical companies have been approved for listing. According to the State Food and Drug Administration, there are more than 10 approved generic drugs with concentrated solution for levetiracetam injection in China, including Huahai Pharmaceutical, Jichuan Pharmaceutical, Yangzijiang Pharmaceutical, Beijing Sihuan Pharmaceutical, Huiyu Pharmaceutical, Puli Pharmaceutical, etc. Among them, the concentrated solution for levetiracetam injection of Puli Pharmaceutical has been approved for marketing in the United States, the Netherlands, Germany, the United Kingdom, Spain and Malaysia.
USBI is facing the crisis of the erosion of levetiracetam's market share. As of the seventh batch of national mining, the antiepileptic chemical drug levetiracetam has been collected in tablets with 250mg specifications, oral solutions 10% (150mL: 15mg) specifications and injection concentrated solutions 5mL: 500mg specifications.
The market for levetiracetam tablets in public hospitals is basically monopolized by the winning enterprises Zhejiang Jingxin Pharmaceutical and Zhejiang Puluo Kangyu. According to PDB data, in the first quarter of 2022, in the market of levetiracetam tablets 250mg, the sales volume of these two Zhejiang pharmaceutical companies in the sample hospital accounted for 92.9%, and the sales amount accounted for 91.8%.
In the levetiracetam oral solution (150mL: 15mg) market, Chongqing Sanhuaxi Pharmaceutical and Yekai Thai Medicine (Suizhou), two enterprises that won the third batch of national procurement, have gradually occupied more markets. From the perspective of sales of enterprises, in the first quarter of 2022, the total sales volume of the two winning bidders in the sample hospital accounted for 94.6%, and the total sales amount accounted for 83.9%.
Zoetiracetam injection concentrated solution 5mL: 500mg specifications included in the third batch of national procurement, there are four enterprises won the bid, Chongqing Shenghuaxi Pharmaceutical won the bid price of 28 yuan / stick, Hainan Puli Pharmaceutical 65.888 yuan / stick, Youshibi 85 yuan / stick, Hebei Renhe Yikang Pharmaceutical 98.5 yuan / stick. In the first quarter of 2022, the total sales volume of the four winning bidders in the sample hospitals accounted for 94.2% and the sales amount accounted for 90.1%, occupying an absolute dominant position. Chengdu Tiantaishan Pharmaceutical, which ranked first in 2020 with 60.7% of sales, only passed the consistency evaluation of the concentrated solution for levetiracetam injection in March 2022, and was not eligible to participate in the collection in 2020, and the proportion of sales in the first quarter of 2022 fell to 8.8%.
Unispec occupies an absolute position in the sales of 500mg specifications, accounting for 96.6% of the proportion, making it still rank first in the sample hospital market of two tablet specifications.
With the deepening of the implementation of the collection, in the case of local enterprises pressing step by step, how much space USE can have in the market of some dosage forms of levetiracetam in public hospitals remains to be seen, and what measures Will Be taken by Usebi in the follow-up will continue to be paid attention to by 21st Century Business Herald reporters.
For more information, please download the 21 Finance APP