The blockbuster targeted anti-cancer drug Fruquintinib that I’ve been following has finally achieved new significant progress recently. According to information on the China National Drug Administration (CNDA, or NMPA), the approval status of the marketing application of Fruquintinib has changed to "Under approval". If everything goes well, Fruquintinib will soon receive the formal approval of CNDA and its marketing within the year is almost certain.

100% Chinese-produced targeted anti-center drug developed by Hutchison MediPharma for 13 years

Fruquintinib is a new, oral, highly selective VEGFR (receptor for vascular endothelial growth factor)-TKI (tyrosine kinase inhibitor) independently developed by Hutchison MediPharma with complete intellectual property, which, by acting on the target of VEGFR kinase family, can well inhibit tumor metastasis and tumor angiogenesis. According to the relevant clinical study, the drug has advantages such as low off-target toxicity, good drug tolerance, and strong action.

The process from a chemical formula to the upcoming marketing of Fruquintinib has taken 13 years. The drug was applied for clinical trial in September 2009, and approved for clinical trial in November 2010. Hutchison MediPharma reached a strategic cooperation agreement with Eli Lilly in October 2013, according to which, Eli Lilly would be responsible for the sales of Fruquintinib in China. Fruquintinib was filed for marketing application in June 2017, and was included in the priority review by reason of "having significant clinical value; major project" in September 2017.

The biggest characteristic of Fruquintinib is 100% Chinese-produced. The drug is the first one developed by a Chinese pharmaceutical enterprise, started clinical study among Chinese patients, and developed through cooperation of Chinese researchers; in simple terms, it is a targeted anti-cancer drug completely developed in a Chinese laboratory. And the drug is also the first new drug independently developed by Hutchison MediPharma in a real sense 15 years after establishment, with the clinical study for treating colorectal cancer approved as a "Major New Drug Invention Project" during the 12th Five-year Plan period of China. And Fruquintinib is also among the first varieties applied for new drug marketing in China’s Marketing Authorization Holder system pilot work.

The longest OS in the third-line treatment history of colorectal cancer (9.30 months)

Treatment of advanced colorectal cancer is based on chemotherapy at present, mainly of combined chemotherapy regimens. Colorectal cancer patients who failed first-line therapies are mainly treated with second-line chemotherapies, however, there is still no subsequent therapeutic regimen for patients who failed second-line standard treatment.

Fruquintinib Phase III clinical study FRESCO was a randomized, double-blind, placebo-controlled, multicenter clinical trial to assess the metastatic colorectal cancer patients who failed at least 2 rounds of treatment (including oxaliplatin, fluorouracil drug, and irinotecan), and the largest pivotal clinical study targeting advanced colorectal cancer so far in China. The study involved 28 research centers in China, and included a total of 416 subjects who were randomized to Fruquintinib group and placebo group according to 2:1 proportion. The study completely met all the predetermined trial endpoints; the median OS of patients in Fruquintinib group was 9.30 months, 2.73 months (P<0.001) significantly longer than that of the placebo group, with death risk reduced by 35% (hazard ratio HR=0.65). Compared to the placebo group, Fruquintinib group patients also had significantly longer PFS (3.71 months vs 1.84 months, P<0.001), reducing disease progression risk by 74% (HR=0.26).

The Phase III clinical study of Fruquintinib obtained the longest survival prolongation in the third-line treatment history of colorectal cancer worldwide. Patients in Fruquintinib group, whether having received anti-VEGF or anti-EGFR treatment or not, could significantly benefit from the drug, with controllable adverse reactions and good safety. In a world, Fruquintinib, the first innovative drug succeeding in third-line treatment of advanced colorectal cancer in China, can become one of the standard therapies as third-line treatment of advanced colorectal cancer.

It's worth mentioning that all the content of the above FRESCO of Fruquintinib was published online on the international authoritative journal: Journal of the American Medical Association (JAMA, IF 47.6) on June 26, 2018, which was China’s first paper on new oncology drug published on JAMA.

Hutchison MediPharma actively laying out the third-line treatment of lung cancer and second-line treatment of gastric cancer

Besides the completed Phase III clinical trial on colorectal cancer treatment, the clinical studies of Fruquintinib underway include third-line treatment of advanced lung cancer and second-line treatment of advanced gastric cancer.

The Journal of Clinical Oncology (JCO) published online all the content of the study results of Phase II clinical trial of Fruquintinib for treatment of advanced NSCLC on March 13, 2018, showing a disease control rate (DCR) of 60.7%. Active exploration has also been conducted for Fruquintinib in terms of gastric cancer treatment; the Phase II clinical trial thereof on the drug combination as second-line treatment of gastric cancer patients showed very good effects, and the Phase III clinical trial thereof has been started. Outside China, a Phase I clinical trial of Fruquintinib has been launched in the U.S.

The tinib market to exceed RMB 10 billion in China in 2018

There have been ten-odd targeted anti-tumor small molecule preparations (tinibs) used clinically in China, with the top varieties separately being: imatinib, gefitinib, icotinib, sorafenib, and erlotinib, of which the sales account for nearly 80% of the overall market. According to the forecast of Southern Medicine Economic Research Institute, the anti-tumor tinib market will exceed RMB 10 billion in China in 2018.

Some insiders are not optimistic about tinib drugs while Chinese pharmaceutical enterprises are flocking to develop tinib drugs, because: 1. The total sales of all the tinib drugs marketed in the world are only a little more than the sales of the drug king Humira, and there is no variety of tinib drugs with annual sales exceeding USD 2 billion except imatinib; 2. Moreover, the indications of tinib drugs are mostly lymphoma, leukemia, and lung cancer; they will have no sales breakthrough if there is no absolute efficacy superiority.

In my opinion, the marketing prospects of Fruquintinib are worth expecting, as Fruquintinib has absolute efficacy superiority in third-line treatment of colorectal cancer, and it is a 100% Chinese-produced drug that has the pioneer status.

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