Gastric cancer drug market broad competition pattern continues to reshape, the giants have poured in

Gastric cancer is the third most common cause of cancer deaths, of which about 15% to 20% of advanced gastric cancer and stomach esophagus carcinoma (especially common in east Asia) is HER2 positive, since the herceptin associated with cisplatin and fluorine pyrimidine in 2010 the FDA approved for first-line treatment, HER2 positive metastatic gastric cancer herceptin relapse after treatment, or her2-negative patients, treatment options are limited.

ADC and dual antibodies to expand the HER2-positive gastric cancer market

Herceptin is about 30% of its revenue comes from the stomach cancer, at present because the patent in the United States, the European Union and China and other major national patent has expired, encounter similar overwhelming hit, Perjeta (duly para bead sheet resistance) and Kadcyla (ADC) resistance by bead odd roche is extended in the field of positive HER2 breast cancer and stomach cancer herceptin important strategy of life cycle, including Perjeta mainly joint herceptin and effective for early or metastatic breast cancer, with herceptin Kadcyla is invalid after early or metastatic breast cancer, but the difference in gastric cancer trials failed to meet the primary end point.

Today for HER2 positive gastric cancer markets main attention focused on the joint development of daiichi sankyo/AZ Enhertu (by bead single ADC), the drug in May 11, the FDA granted qualification (BTD), breakthrough drugs used to treat have previously received at least two kinds of solutions, including by bead sheet resistance, HER2 positive patients with adanced G/GEJC, daiichi sankyo indications have on May 7, the filing in Japan, based on the phase II clinical trials, called DESTINY - Gastric01 Enhertu significantly improved OS (12.5vs.8.4 MOS, HR=0.59) and PFS (5.6 vs.3.5 MOS, HR=0.47) compared with chemotherapy regimens (paclitaxel or irinotecan monotherapy).

Herceptin plus chemotherapy after first-line treatment for metastatic gastric cancer progress choice is not much, although in 2014, lilly's ramucirumab approved in the United States listed after chemotherapy on the HER2 positive or negative second-line treatment of gastric cancer, after roche Kadcyla and novartis Lapatinib in HER2 positive gastric cancer second-line treatment trials, relative to the chemotherapy did not show significant survival benefit, so produced a hypothesis, gastric cancer patients after once herceptin treatment failure, would not be capable of responding to other HER2 targeting therapy, However, the success of Enhertu as a third-line treatment has proved that it can still show activity after the failure of Herceptin, which undermines this assumption. The DESTINY-Gastric02 trial is currently under way as a second-line treatment.

In addition, two Chinese pharmaceutical companies have introduced antibody products. The HER2 bi-specific antibody zanidatamab developed by Zymeworks, based on its Azymetri platform, can simultaneously bind two non-overlapping HER2 epitopes, namely double complementary binding, which can double block HER2 signal, enhance binding and remove HER2 protein on the cell surface. The exclusive development and commercialization rights in Asia (excluding Japan), Australia and New Zealand were introduced by Baekshiar in November 2018. This year, orphan her2-positive gastric cancer drugs were awarded in the United States and the European Union, while the FDA also awarded Zanidatamab combined with standard chemotherapy as a fast-track first-line treatment for gastroesophageal junction adenocarcinoma. The previously published stage I results showed that HER2 was positive for both FISH and gastroesophageal adenocarcinoma, with ORR=85% (17/20) and PR=55% (11/20).

Zanidatamab expression in HER2 tumor species development program

The other is MacroGenics' Fc optimized HER2 monoclonal antibody, Margetuximab, to enhance its immune system involvement and enhance lethality against cancer cells through antibody-dependent cell-mediated cytotoxicity (ADCC). In 2018, Zaiding Pharma received exclusive development and marketing licenses for Margetuximab and Tebotelimab in greater China, including the Mainland China, Hong Kong, Macau and Taiwan. In June of this year, Margetuximab received FDA approval for an orphan drug for gastroesophageal cancer, and the results of a phase IB/II clinical trial of Margetuximab combined with pablizumab showed a disease control rate (DCR) of 53% for CR, PR, and stable disease (SD) (49/92 patients). The median PFS was 2.7 months, and the median OS was 12.5 months. The subgroup analysis found that patients amplified with HER2 IHC3+, PD-L1+ and HER2 had the best efficacy, with AN ORR of 80%.