On October 16^th, 2019, the clinical results of ensartinib hydrochloride, an anaplastic lymphoma kinase (ALK) inhibitor, were published on The Lancet Respiratory Medicine, an internationally recognized top-tier medical journal. In the same issue, Dr Ross Camidge, an oncologist and a professor at the University of Colorado cancer center, commented that through taken only once per day, ensartinib had a clear efficacy and a good safety profile, and it could be the second-line choice of treatment for advanced lung cancer patients with ALK mutations, or a potential first-line choice of treatment. Previously, Dr Camidge praised the clinical results of icotininb hydrochloride in an editorial in 2013. The publication of ensartinib’s clinical results indicates that a new drug from Betta is recognized by the international medical community.

Lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), in which NSCLC accounts for 85% of the patient population. The hyperactivation of the ALK pathway was one of the main mechanisms for NSCLC. Currently, the targeted therapy launched in China for ALK+ NSCLC patients is the first-generation ALK inhibitor crizotinib, but most of the patients have developed drug resistance and their disease progressed within a year. Ensartinib has a higher affinity with ALK than crizotinib, and it can overcome crizotinib resistance. The phase II single-arm and multiple-center clinical study of ensartinib was led by Prof. Li Zhang from the Sun Yat-sen University Cancer Center to evaluate the efficacy and safety of ensartinib hydrochloride on ALK+ NSCLC patients, and the study has recruited 27 clinical sites in China. The study enrolled the advanced or metastatic ALK+ NSCLC patients who were over 18 years old and their disease had progressed after the treatment of crizotinib. The primary endpoint of the study was the objective response rate (ORR) evaluated through the independent central review (ICR).

The clinical study has enrolled 160 patients. It indicated that ensartinib has good efficacy and safety profiles on ALK+ NSCLC patients who have developed resistance to crizotinib. By the end of mid-September, 2018, the study has reached an overall ORR as 52%, a median PFS as 9.6 months and an intracranial ORR as 70%. The updated data showed the good continuous results with an overall ORR as 52.6%, the disease control rate as 87.8%, the median PFS as 11.2 months, an intracranial ORR as 71.4% and the intracranial lesion control rate as 95.2%. For the safety profile, the most common adverse events (AE) were rash and increasing ALT and AST, which could be relieved through treatment discontinuation or relevant treatment. The clinical study proved ensartinib’s superiority in efficacy with higher intracranial response rate and in safety with manageable AEs compared to other ALK-targeting molecules. The study also indicated that ensartinib has shown activities in multiple ALK mutations including G1269A、F1174、C1156Y and T1151, and mutations that causes drug resistance to ceritinib and alectinib. Though this discovery requires further confirmation, it shows that ensartinib can broaden the activity spectrum of second generation ALK inhibitor and provides an alternative to patients.

The Lancet Respiratory Medicine – with an impact factor of 22.992 – is a top-tier journal affiliated with The Lancet and publishes research studies in respiratory medicine and intensive care such as asthma, chronic obstructive pulmonary disease, tobacco control, critical respiratory illness, lung cancer, cystic fibrosis, respiratory and pulmonary infections, etc.. The journal coverage includes but not limited to original research, review, comments and news. The publication of ensartinib’s phase II study demonstrates that the clinical research capability of Chinese researchers has reached the international level, and furthermore proves the efficacy and safety of ensartinib, promoting ensartinib at the global stage and illustrating the R&D investment of Betta.

Prof. Li Mao, SVP & CMO of Betta, commented that the publication of ensartinib’s phase II clinical study on The Lancet Respiratory Medicine is exciting and showed the group efforts from Betta’s team. Ensartinib's market launch preparation in China has attracted global attentions, and it has been granted a priority review by the NMPA. At present, Betta is fully cooperating with the regulatory agency to prepare for its market launch, and looks forward to providing patients with a new and effective treatment option. Betta is also carrying out multiple clinical studies globally. Among them, a global multi-center phase III clinical trial of a head-to-head comparison of ensartinib with crizotinib for ALK+ NSCLC patients is progressing smoothly and is expected to become the first innovative drug developed independently and launched globally by a Chinese pharmaceutical company. Betta's mission is to develop more affordable medications, fulfill more unmet medical needs, and benefit more patients.

About Ensartinib hydrochloride

Ensartinib hydrochloride is a novel, potent and highly selective next-generation ALK inhibitor, and is developed jointly by Betta and its subsidiary Xcovey Holding, Inc. (Xcovery). Ensartinib targets locally advanced or metastatic ALK+ NSCLC patients whose diseases have progressed after crizotinib treatment. Since there is no domestically developed ALK inhibitor approved in China, ensartinib will fulfill the unmet medical needs of Chinese patients.

About Betta

Betta Pharmaceuticals Co., Ltd. (Stock code: 300558.SZ) is a national level high-tech enterprise, established by the experienced talent team of overseas returnees, with research and development (R&D) of innovative drugs as its core focus, integrating R&D, manufacturing and marketing. The company independently developed China's first small-molecule targeted anticancer drug, icotinib hydrochloride (trade name: Conmana). It was recognized as a major breakthrough in the Chinese public healthcare industry and has won China Patent Gold Award twice as well as the first National Scientific and Technological Progress Award in China's chemical and pharmaceutical industry. Until the third quarter in 2019, icotinib has benefited 230,000 patients of advanced lung cancer, with the cumulative sales reaching nearly 7 billion RMB. The company has established a comprehensive new drug R&D platform, with its R&D centers in Hangzhou and Beijing, and more than 30 innovative drugs under development, covering multiple tumor indications such as lung cancer, renal cancer, and breast cancer. The company has also reached strategic collaboration with leading domestic and foreign pharmaceutical companies such as Amgen, Xcovery, Tyrogenex, Merus, Mabworks, and InventisBio, to work together to promote the health and well-beings of the general public.