Takeda's Brentuximab Vedotin Becomes China's Second Approved ADC Therapy

Text | Xiao Yaowan

On May 13, the NMPA official website announced that Takeda Pharmaceutical’s marketing application for brentuximab vedotin for injection in China had been approved, making it the second antibody-drug conjugate (ADC) drug to be marketed in the country.

Source: CDE

Market launch set 3 records

Brentuximab vedotin is an antibody-drug conjugate (ADC) jointly developed by Takeda Pharmaceutical Company Limited and Seattle Genetics.

In 2011, brentuximab vedotin for injection was approved by the FDA and launched in the United States under the brand name Adcetris. Its market entry set three records: it is currently the only marketed antibody-drug conjugate (ADC) targeting CD30; it is the first new drug approved by the FDA in nearly 40 years for anaplastic large cell lymphoma (ALCL); and it is the first first-line treatment drug for classical Hodgkin lymphoma (cHL) and peripheral T-cell lymphoma (PTCL).

Currently, brentuximab vedotin has been approved for multiple indications in the United States, including classical Hodgkin lymphoma (cHL), anaplastic large cell lymphoma (ALCL), peripheral T-cell lymphoma (PTCL), and mycosis fungoides (MF).

Significant Efficacy

Structurally, brentuximab vedotin consists of three components: the CD30-targeting monoclonal antibody brentuximab, the microtubule-disrupting agent monomethyl auristatin E (MMAE), and a dipeptide linker composed of citrulline and valine.

After injection into the body, brentuximab vedotin, guided by the CD30 antibody, locks onto and binds with CD30-positive cancer cells. It then enters the cells, where the dipeptide linker is cleaved in the lysosomes, releasing MMAE to exert its tumor-killing effect.

Clinical study results demonstrate that, compared with existing chemotherapy regimens for relapsed/refractory classical Hodgkin lymphoma (cHL) and systemic anaplastic large cell lymphoma (ALCL), brentuximab vedotin significantly prolongs patient survival, increasing the 5-year survival rates to 41% and 60%, respectively.

The Second ADC Drug Approved for Marketing in China

Novel Targeted Drugs with High Efficacy and Low Toxicity. Antibody-Drug Conjugates (ADCs) link monoclonal antibodies with drugs, enabling the targeted delivery of the drug to specific sites via the antibody. Combining precise targeting with potent cytotoxicity, ADCs represent a key area of research in oncology therapeutics.

In September 2016, Takeda initiated a Phase II clinical trial of brentuximab vedotin in China. The study was originally planned to enroll 30 participants, but ultimately enrolled 39. The primary endpoints were the overall response rate (ORR) at the end of treatment and safety. The primary objective was to evaluate the efficacy and safety of brentuximab vedotin in Chinese patients with relapsed/refractory CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). The secondary objective was to assess the pharmacokinetics (PK) and immunogenicity of brentuximab vedotin in these patients.

In April 2019, Takeda submitted the marketing application for brentuximab vedotin in China, and it was included in the priority review and approval list by the Center for Drug Evaluation (CDE) in June. Based on clinical trials conducted domestically, the indication applied for brentuximab vedotin in China is relapsed/refractory CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL).

At the 2019 CSCO Annual Meeting, Peking University Cancer Hospital presented therapeutic data for this drug in the Chinese patient population: Brentuximab vedotin demonstrated an overall response rate of approximately 70% in patients with classical Hodgkin lymphoma (cHL) and systemic anaplastic large cell lymphoma (sALCL), with favorable long-term follow-up data on progression-free survival (PFS) and safety.

On January 21, 2020, Roche received approval from the National Medical Products Administration for market launch in China. As monotherapy, it is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant therapy based on taxanes combined with trastuzumab, becoming the first HER2-targeted ADC product in China.

With this approval, brentuximab vedotin becomes the second ADC drug approved for marketing in China, following Roche’s trastuzumab emtansine.

Market Landscape of ADC Drugs in China

To date, the FDA has approved six antibody-drug conjugate (ADC) drugs for marketing. Statistics show that more than 60 ADC projects worldwide have entered the clinical research stage, covering indications such as urothelial carcinoma, triple-negative breast cancer, HER2-positive breast cancer, and glioblastoma.

In the Chinese market, in addition to the two drugs already launched, Pfizer has submitted a marketing application for inotuzumab ozogamicin, which is expected to become the third antibody-drug conjugate (ADC) drug approved in China. In the race for ADC research and development, more than 10 domestic pharmaceutical companies, including Bio-Thera Solutions, Jiangsu Hengrui Medicine, Kelun Pharmaceutical, Zhejiang Medicine, Shanghai Pharmaceuticals, and Fudan-Zhangjiang Biopharmaceutical, have made strategic layouts. Most of the ADC drugs under development target HER2, with indications covering breast cancer, gastric cancer, and non-small cell lung cancer (NSCLC). Among them, BAT8001, developed by Bio-Thera Solutions, is progressing the fastest and is currently in Phase III clinical trials for HER2-positive advanced breast cancer. It is expected to complete the clinical study summary report and submit a New Drug Application (NDA) in China in 2021.