The TKI Lung Cancer Market in China

In the recent years, the morbidity and mortality rate of lung cancer has been riding on a steady upward trend to top the list of all cancers globally. China is no exception. With an annual growth rate as high as 26.9%, lung cancer is currently the leading malignant tumor in China.

The market size of lung cancer drugs has also been growing at a rapid speed. From 2010 to 2015, it nearly tripled in China, reaching a total of $3.3 billion (1 US dollar = 6.77 Yuan). Its annual compound growth rate has amounted to 21.13%. And the market is expected to grow further this year, when its total size is estimated to pass $4.43 billion, primarily thanks to the launch of new anticancer drugs and the inclusion of some targeted lung cancer medications into the national medical insurance drug list.

So far, a number of methods can be applied to treat lung cancers, including surgical removal, radiation, chemotherapy, biologics, immunotherapy, etc. Among them, the combination therapy of carboplatin or cisplatin with taxol or gemcitabine is still widely accepted as the first-line treatment, whereas, targeted small molecule TKIs (tyrosine-kinase inhibitors) are commonly used in the second line. However, thanks to its excellent efficacy, TKI is gradually taking over the market to become the most popular option for lung cancers.

The rising of small molecular targeted lung cancer drugs

From 2013 to 2017, the US FDA greenlighted a total of 10 lung cancer drugs for the market. Among them, five are small molecule targeted drugs: Gilotrif from BI, Zykadia from Novartis, Tagrisso from AstraZeneca, Alecensa from Roche, and Alunbrig from Takeda. All except Alunbrig have reached the Chinese market and their estimated market size surpassed $738 million in 2017.

No.

Produce name

Company name 

Applications

1

Gefitinib

AstraZeneca

The first-line treatment for metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations

2

Icotinib

Beta Pharma

The second-line treatment for advanced NSCLC

3

Lenvatinib

Eisai/Merck

The first-line treatment for unresectable hepatocellular carcinoma (HCC); Other indications include lung cancers and solid tumors

4

Erlotinib

Roche

The treatment for metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or ≥second-line treatment after progression following at least 1 prior chemotherapy regimen

5

Apatinib

Hengrui Medicine

The treatment for stomach cancer, non-squamous NSCLC, liver cancer, etc.

6

Crizotinib

Pfizer

The treatment of metastatic NSCLC with anaplastic lymphoma kinase (ALK)-positive or ROS1-positive

7

Afatinib

BI

The first-line treatment for metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations

All lung cancer TKIs in the Chinese market.

At present, three generations of EGFR (epidermal growth factor receptor) TKI have been developed against lung cancers. The first generation includes gefitinib, erlotinib, and icotinib. They bind with EGFR reversibly and compete with ATP (adenosine triphosphate) to inhibit the activation of EGFR.

However, with the second and third generations hitting the scene, the first-generation TKI is gradually being replaced. The second-generation TKI is an improvement on the first generation. It is characterized by its irreversible binding with EGFR, reducing the risk of drug shedding, and thus preventing disease progress. But this is a double-edged sword. It also leads to severe side effects. Many patients stop the regimen because of intolerable diarrhea, rash, etc. Therefore, from the perspective of clinical effects, the second-generation TKI has limited improvements. In a head-to-head trial with the first generation of TKI gefitinib, the second-generation afatinib did not show significant clinical advantages.

The third -generation TKI has corrected this pain point and reduced the side effects significantly. Its clinical results are outstanding. Worth noting is that the third-generation TKI includes osimertinib. It can bind with the narrow T790M mutation structure through its small binding region, making it especially useful to target at T790M gene resistance after treatment. For these patients, it is the only effective medication so far.

The market potential of TKI is huge in China. While its applications in various diseases broaden, it is expected to grow into a total of $1.77 billion. Up to now, a number of Chinese pharmaceutical companies have made their way into this space, such as Chiatai Tianqing, Kelun, CSPC, Betta Pharma, and Hansoh.

Product type

Number of companies developing it

Representatives

Gefitinib generics

11

Kelun, CSPC, Medchk, etc.

Erlotinib generics

5

Acebright, Chiatai Tianqing, Jiangsu Wanguard Pharmaceutical, etc.

Afatinib generics

4

Chiatai Tianqing, Hansoh, Kelun, etc.

Innovative TKIs

10

ACEA Pharma, Betta Pharma, etc.

Gefitinib: China’s leader in lung cancer-targeted drugs

Gefitinib, a first-generation TKI, can selectively inhibit the activity of EGFR tyrosine kinase. It can restrain the proliferation of tumor cells, metastasis, and neovascularization, thus curbing the symptoms of metastatic non-small cell lung cancer and increasing the survival rate.

In February 2005, AstraZeneca brought it to the Chinese market. It has demonstrated to be particularly effective on patients of Asian descent without smoking histories. The total usage of gefitinib in public hospitals has reached $36.78 million, representing about 28.05% of the lung cancer-targeted small molecule drug market. After joining the national medical insurance list in China, its growth is expected to rise further.

Icotinib: the main driving force

With the launch of China’s domestic TKI, the size of the small molecule targeted drug for lung cancer is expanding year by year. Domestic players have become the rising stars.  Among them is the first-generation TKI icotinib from Betta Pharma. It is the first self-developed, small molecule-targeted anti-cancer drug with complete independent intellectual property rights. Currently, it has been approved to treat the advanced non-small cell lung cancer.

Icotinib is equipped with a wide range of patents from China, America, and other countries. Its chemical structure, molecular mechanism, and effects are similar to gefitinib and erlotinib, but with superior safety profiles.

The total sales volume of icotinib in Chinese public hospitals was about $31.61 million in 2016, accounting for about 24.10% of the lung cancer small molecule targeted drug market. However, with a range of targeted medicines join the national medical insurance list, icotinib will face challenges in the future.

Anlotinib: the dark horse

Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor. It can effectively restrain the activity of a series of enzymes, including VEGFR, PDGFR, FGFR, c-Kit, etc., leading to its dual effects of anti-tumor angiogenesis and tumor growth inhibition.

It is self-developed by Chiatai Tianqing. On May 9, 2018, it was officially approved by the Chinese FDA and entered the market.

So far, anlotinib is the only effective single-agent oral drug used in advanced non-small cell lung cancers. Its adverse reactions are mild and well tolerated among patients. At present, it is expected to become a standard third-line treatment for patients with advanced NSCLC.

According to the clinical results, anlotinib does not only work on non-small cell lung cancers. It can also be used to treat a variety of other cancers, including soft tissue sarcoma, ovarian cancer, etc. Currently, Chiatai Tianqing is actively conducting multicenter clinical trials on these targets across the globe.

Avitinib: the first China-developed third generation TKI

Avitinib is a third-generation EGFR TKI developed by ACEA Pharma. It is also the first third-generation TKI self-developed in China.

According to its animal model and Phase I clinical trial data, it has shown an excellent safety profile and strong efficacies. Particularly, its disease control rate is as high as 90%, comparable to the famous Targrisso from AstraZeneca.

Currently, it is under process to meet with CFDA/CDE approval on the basis of its Phase II single-arm trial.

Honorable mentions

Qilu Pharmaceutical’s generic gefitinib was approved by CFDA in July 2017, marking the first China-developed gefitinib in history. Gefitinib is developed on the basis of the original gefitinib by AstraZeneca and has further improved its synthesis process. Its price is about 1/3 lower than the original. The product has achieved major success, last year, it has netting a total of $76.81 million. It is expected to exceed $147.71 million in 2018.

Another honorable mention is the generic erlotinib from Acebright. It is currently under CFDA review and on the track to become the first China-developed erlotinib generic.

Big molecules open up new possibilities

Other than TKI, bevacizumab is a rising star in the field of lung cancer.

Bevacizumab, developed by Roche, is the first humanized monoclonal antibody against vascular endothelial growth factor (VEGF). In 2015, it was approved by the CFDA for treating lung cancer patients.

Research has shown that combination therapy of bevacizumab and chemotherapy-containing platinum has achieved significant results when used to treat Chinese non-squamous NSCLC patients as the first-line treatment. It has managed to extend both their progression-free survival and overall survival. Bevacizumab has kickstarted biologic treatment in lung cancer treatment and has a potential to become an important regimen for lung cancer patients down the line.

The market for use of bevacizumab in public hospitals in China’s major cities reached a total of $53.18 million in 2016. It increased about 37.43% compared to the same period in 2015. In 2017, bevacizumab was included in the national medical insurance drug list. It is expected that its market will further grow in China, which has brought tremendous pressures to China’s domestic TKI providers.

Other than bevacizumab, PD-1/PD-L1 antibodies, the superstar in the cancer treatment, have also shown huge potential. Since 2016, they have been approved to treat lung cancers one after the other, including Opdivo from BMS, Keytruda from Merck, Tecentriq from Roche, Cyramza, and Portrazza from Eli Lily.

Jin Zhang M.D., Ph.D is project and account manager at LakePharma, and editor at The Pharmaceutical Consultant.