On November 19, 2020, the latest approval document released by the National
Medical Products Administration (NMPA) showed that Ensartinib Hydrochloride
(approval numbers: CXHS1800045, CXHS1800046), a Class 1 innovative drug
developed by Betta Pharmaceuticals, was officially approved for marketing. It
has become the first domestically developed and independently innovative
anaplastic lymphoma kinase (ALK) inhibitor in China.
Ensartinib Hydrochloride (code name: X-396) is a novel, highly potent and highly selective next-generation ALK inhibitor jointly developed by Betta Pharmaceuticals and its wholly-owned subsidiary Xcovery Holdings, Inc. It is a molecular entity compound with completely independent intellectual property rights. Compared with crizotinib, ensartinib forms an additional hydrogen bond when binding to the ALK target protein.
On December 26, 2018, the new drug application (NDA) for ensartinib was officially accepted by the NMPA. The approved indication is for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are positive for ALK rearrangement and have either progressed after treatment with crizotinib or are intolerant to crizotinib.
The approval of ensartinib hydrochloride for drug registration is based on the phase II single-arm, multicenter clinical study entitled "Efficacy and Safety Evaluation of X-396 Capsules in the Treatment of Crizotinib-Resistant ALK-Positive Non-Small Cell Lung Cancer Patients". The results of this clinical study demonstrated that ensartinib hydrochloride has favorable efficacy and safety profile in patients with crizotinib-resistant ALK-positive NSCLC.
According to the results of a multicenter, phase II clinical study published in The Lancet Respiratory Medicine in October 2019, which aimed to evaluate the efficacy and safety of ensartinib in ALK-positive NSCLC patients who failed crizotinib treatment: among 147 patients with measurable target lesions, the objective response rate (ORR) reached 52%, the disease control rate (DCR) was 93%, and the median progression-free survival (PFS) was 9.6 months. Meanwhile, ensartinib also exhibited prominent central nervous system (CNS) activity. Among 40 patients with evaluable CNS lesions, the ORR was 70%, the DCR was 93%, and the median duration of response (DOR) was 8.6 months. Both the overall efficacy and intracranial efficacy showed favorable and durable outcomes.
In addition, the global multicenter phase III clinical trial (eXalt3) of ensartinib for the first-line treatment of ALK-positive NSCLC patients has completed data lock-up. The top-line results were first presented by Professor Lena Horn, the principal investigator (PI) of the clinical trial, at the Presidential Symposium of the World Conference on Lung Cancer (WCLC) in August 2020. The results showed that among 290 enrolled ALK-positive NSCLC patients, the complete response (CR) rate of ensartinib was 14% versus 6% for crizotinib; the overall response rate (ORR) was 75% versus 67% for crizotinib; the median PFS was 25.8 months versus 12.7 months for crizotinib; and the intracranial response rate was 64% versus 21% for crizotinib.
Ensartinib also initiated a phase II clinical study for the treatment of ALK-positive advanced malignant melanoma in the United States in December 2017, which is the world's first clinical study exploring ALK inhibitors for melanoma treatment. If successful, it is expected to be approved for marketing as an orphan drug. In addition, an indication for non-Hodgkin's lymphoma is currently under clinical development. The global and domestic development status of its investigational indications is shown in the figure (not provided herein). Unfortunately, due to the failure to meet the expected efficacy in the interim analysis, Betta Pharmaceuticals voluntarily suspended the phase II clinical study of ensartinib for the indication of ROS1-positive NSCLC in June 2020.
