The 1st Chinese-produced Biosimilar Approved for Marketing

The National Medical Products Administration of China (NMPA) released the news on Feb. 25 that the Rituximab Injection (trade name: Hanlikang) under Shanghai Henlius Biotech, Inc. has been approved for marketing. This is of a milestone meaning as it is the approval of the first Chinese-produced biosimilar, which has rapidly aroused heated discussions in the medical world.

We would wonder: why rituximab is the first Chinese-produced biosimilar? In fact, we would find out the reason if we looked into the situation of the original drug of rituximab: because this original drug is too excellent!

Originally developed by Genentech, Inc. (Roche), rituximab is the first monoclonal antibody approved by FDA for cancer treatment, which is mainly used to treat non-Hodgkin lymphoma. Rituximab has been among the global top 10 drugs by sales in recent years owing to its distinct efficacy, showing its leadership.

Let’s first see the list of global top 10 drugs by sales in 2018. We can see from Fig. II that sales of Rituxan reached USD3.483 billion in 2018, ranking fifth in the list. And certainly, this was not the best performance of Rituxan, which ranked among the top 3 in 2017, with sales of up to USD7.935 billion!

Fig. II Global Top 10 Drugs by Sales in 2018

We can also see from Fig. II that among the top 10 drugs, there are only two small molecule drugs, i.e., Eliquis and Revlimid, and biological drugs account for 80%, especially that the monoclonal antibody drugs account for 70%, therefore, the imitation of those excellent monoclonal antibodies is a work focus of the global generic drug enterprises.

Furthermore, we can also see that Roche occupies 3 positions in the list of top 10, being the pharmaceutical enterprise with the largest number of drugs listed, with all the listed drugs being monoclonal antibodies, showing that biological drugs including monoclonal antibodies have been developing rapidly in recent years and become a battleground of the pharmaceutical enterprises and online medical supply companies.

Fig. III Global Top 10 Drugs by Sales in 2014-2018

Fig. III shows the global top 10 drugs by sales from 2014 to 2018, according to which, rituximab (Rituxan) had stayed high in the list of top 10 for years and was even among the top 3 in 2015 and 2017. In fact, we can also find out by further query that rituximab (Rituxan) had been in the list of global top 10 drugs by sales in the decade from 2009 to 2018, which brought many profits to Roche and benefits to innumerable patients, and this decade could be called its "golden decade"!

Therefore, it makes sense that so many pharmaceutical enterprises want to imitate such an excellent monoclonal antibody drug. It’s reported that in China alone, there have been more than 10 pharmaceutical enterprises that have conducted imitation research on it, including Henlius, Sunshine Guojian, Hisun Pharmaceutical, Chiatai Tianqing, Innovent Biologics, Hualan Biological, and Livzon, etc. As one of the enterprises earliest in making rituximab biosimilar, Henlius has used the high-expressing cell lines, to increase the yield of the averagely 1g/L monoclonal antibody of cell line to 3g/L, and used the advanced single-use manufacturing process; and it has also independently developed the cell culture media, and considered aspects such as plant and capacity, which will make the biosimilar have great advantages over the imported original drug in terms of price.

The development of biosimilars of biological drugs such as monoclonal antibodies is quite difficult due to the high complexity thereof, however, thanks to the rapid development of the biotechnology of China in recent years, the biological drug development has been changing rapidly in China in recent years. Although it has been 4 years since China officially introduced the biosimilar regulation document—Technical Guideline for Development and Evaluation of Biosimilars (Interim) in 2015, rituximab (Rituxan) is obviously a good start for biosimilars in China and provides precious experience, being a milestone development of "from nothing to something" and "from zero to one".

About  the Author:    

Yuntian, Ph.D. in medicinal chemistry, is mainly engaged in small molecule drug research, especially good at small molecule drug synthesis process and later stage drug development research. He has completed the synthesis and activity evaluation of multiple anti-cancer drug molecules. 

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