Research and development of a brother Hengrui-paclitaxel data suspected of fraud

September 2017. A report letter to the "* * City Food and Drug Administration" was published. The whistleblower claimed that he had worked in * * company and had experienced and witnessed the falsification of the company's paclitaxel albumin declaration materials.

The whistleblower said, "Through three batches of fraud in the pilot test in the process of pharmaceutical research and development, the pharmaceutical company successfully obtained the absolute advantage in the registration time of the product, obtained the first imitation qualification, and applied for the qualification of 1.6 new drugs", while "the same variety of research and development enterprises, including CSPC, Hunan Kelun, Qilu Pharmaceutical, Zhengda Tianqing, Zhejiang Haizheng, etc, it is only in the clinical stage of declaration", and finally concluded that the benefits obtained by the pharmaceutical company through fraud in the process of pharmaceutical development can be seen.

Although the letter did not explicitly mention the name of the reported pharmaceutical company from beginning to end, in fact, a discerning person can see at a glance that its Jianfeng refers to Hengrui Pharmaceutical, which is considered by the industry to be the "first brother of research and development. The whistleblower said that based on the fake data, the company obtained a copy of the product registration and registered a new drug for the new indications of the product in advance.

And then there is the formal intervention of the drug administration. The "Complaint Report Reply" issued by the Shanghai Food and Drug Administration shows that Shanghai Hengrui Pharmaceutical Co., Ltd. submitted an application for registration of the anti-tumor generic drug "Paclitaxel Albumin" in accordance with the 6 categories of chemical drugs, but the pharmacy application The data in the materials are related matters fabricated. The bureau organized relevant departments to conduct special studies and appointed inspectors to Shanghai Hengrui to conduct field investigations, and with the "paclitaxel albumin" (paclitaxel for injection (albumin binding type)) project leader to understand and verify the relevant situation.

It has been verified that paclitaxel for injection (albumin binding type) is jointly developed by Shanghai Hengrui and Jiangsu Hengrui, of which Shanghai Hengrui is responsible for small-scale and pilot-scale research and development, and Jiangsu Hengrui is responsible for process verification, production scale sample preparation and follow-up research and declaration. In April 2013, Jiangsu Hengrui, as the registration applicant, submitted an application for generic drug registration of paclitaxel for injection (albumin binding type) (chemical drug category 6) to the Jiangsu Food and Drug Administration. The Jiangsu Provincial Bureau carried out the acceptance, on-site verification, review and reporting of the application.

According to the relevant provisions of the measures for the Administration of Drug Registration, the applicant is responsible for the authenticity of all the materials in the application for variety registration. Since the applicant for the registration of paclitaxel for injection (albumin-bound) is not in the administrative jurisdiction of Shanghai, the Shanghai Food and Drug Administration cannot further apply for the registration of this variety. It is recommended to report to the Jiangsu Food and Drug Administration.

Judging from the current processing results, it will take some time for Hengrui to have a clear result on whether Hengrui really falsified the data on the registration application for paclitaxel for injection (albumin binding type) in the short term. However, for Hengrui, it is extremely important to prove its innocence, which is not only related to the progress of priority review and approval, but also directly affects the future market performance of this blockbuster product with expected sales of more than 1 billion yuan.

What is paclitaxel?

As a global blockbuster dosage form, paclitaxel (albumin-bound) was developed by Abraxis BioScience Company of the United States and was approved by FDA in 2005. Its trade name is Abraxane. In 2010, Celgene Company acquired Abraxis with a down payment of US $2.9 billion, thus bringing the Abraxane into the bag. According to Southwest Securities, the first approved indication in Abraxane is metastatic breast cancer, which has been extended to non-small cell lung cancer and pancreatic cancer. With the continuous expansion of indications, the sales of this variety continue to rise, with global sales of US $1.16 billion in 2016, and global sales of this variety are expected to exceed US $2 billion in 2020.

Its good market performance is partly due to its optimization and improvement of traditional paclitaxel dosage forms. Compared with traditional dosage forms, it has the advantages of better efficacy, excellent water solubility and lowest toxic and side effects. Because of its low side effects, the dosage form can increase the tolerated dose of the patient, and the increase in the tolerated dose also increases the therapeutic effect of paclitaxel.

In the domestic market, Abraxane was declared imported in China in 2006, and was approved by CFDA in 2008 for domestic marketing. It is used to treat metastatic breast cancer that failed combined chemotherapy or breast cancer that recurred within 6 months after adjuvant chemotherapy. Other indications are still Not approved. According to IMS statistics, Abraxane domestic sales in 2016 are about 0.32 billion yuan, and the domestic market is still in the stage of volume.

This also makes it a popular generic variety of domestic mainstream large pharmaceutical companies. According to the report of Southwest Securities, there are currently 7 domestic enterprises that have declared this variety, including Haizheng Pharmaceutical, Hengrui Pharmaceutical, Qilu Pharmaceutical, Shiyao Group, Zhengda Tianqing, Kelun Pharmaceutical, Jiangsu Kanghe Biology, etc. Among them, Hengrui and Shiyao have made the fastest progress. According to the 20th batch of priority review notice issued by CDE, the registration application of Hengrui Pharmaceuticals and Stone Pharmaceutical Group has been included in the priority review notice, which indicates that the final stage of review and approval of production report has been officially entered. It is precisely because of this that once Hengrui Pharmaceuticals is confirmed at this stage that there is indeed a problem of data falsification in the declaration process, it will undoubtedly have a huge impact on the progress of the product on the market and the competitiveness of the paclitaxel market.

Generally, those who are always used to being "targeted" belong to the star enterprises in the industry. They play an important role in the industry, and to some extent, they can even represent the direction of the development of the industry. It is a positive thing to pay attention to such companies. However, from the perspective of enterprises, the best way to deal with concerns with special purposes is to strengthen their own capability construction. Whether it is to strengthen the awareness of intellectual property protection or to study their own relevant declaration data, it will help the enterprise's own development.