Breaking News! The Second ADC Approved for Marketing in China

According to the NMPA website on May 13, the marketing application for Brentuximab Vedotin Injection filed by Takeda Pharmaceutical in China has been reviewed and approved, to become the second ADC approved for marketing in China.

3 records set in its marketing

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

Brentuximab Vedotin Injection was approved by the FDA for marketing in the U.S. in 2011, with the trade name being Adcetris. The marketing of this drug set three records: the only marketed CD30-targeted ADC, the first new drug approved by the FDA for anaplastic large cell lymphoma (ALCL) in recent 40 years, and the first first-line treatment for classical Hodgkin lymphoma (cHL) and peripheral T-cell lymphoma (PTCL).

Brentuximab vedotin has been approved a variety of indications in the U.S., including cHL, ALCL, PTCL, and mycosis fungoides (MF), etc.

Significant efficacy

Structurally, brentuximab vedotin consists of three parts: CD30-targeted monoclonal antibody brentuximab, microtubule disruptor MMAE (monomethyl auristatin E), and citrulline-valine dipeptide linker.

Once injected into the body, navigated by the anti-CD30 antibody, brentuximab vedotin locks and binds onto cancer cells that carry CD30, enters the cells and disconnects the dipeptide linker at the lysosome to release MMAE that kills the tumor.

According to a related clinical study, compared to existing chemotherapy regimens for relapsed/refractory cHL and ALCL, brentuximab vedotin could significantly increase patients’ survival, with the 5-year survival of patients in the treatment groups separately increasing to 41% and 60%.

Second ADC approved for marketing in China

ADCs, as new targeted drugs with high efficacy and low toxicity, link monoclonal antibodies to drugs and directly deliver drugs to the targets via the antibodies. ADCs have both targeting and high killing abilities and represent a key research direction for oncology drugs.

Takeda launched a phase II clinical trial of brentuximab vedotin in China in Sep. 2016, which planned to recruit 30 people and eventually recruited 39, with the primary endpoint being the overall response rate (ORR) and safety at the end of treatment, the primary objective being the evaluation of the effectiveness and safety of brentuximab vedotin in Chinese patients with relapsed/refractory CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL) and the secondary objective being the evaluation of the PK and immunogenicity of brentuximab vedotin in Chinese patients with relapsed/refractory CD30-positive HL or sALCL.

In Apr. 2019, Takeda filed the marketing application for brentuximab vedotin in China, which was included in the list subject to priority review and approval by the CDE in June of the same year. Based on the clinical trial conducted in China, the indication applied for brentuximab vedotin in China was relapsed/refractory CD30-positive HL or sALCL.

At a meeting of the CSCO in 2019, the therapeutic data of this drug in the Chinese patient population were published by the Beijing Cancer Hospital: the ORR of brentuximab vedotin in cHL and sALCL patients reached about 70%, with good progression-free survival (PFS) and safety data at long-term follow-up.

Roche was approved by the NMPA on Jan. 21, 2020 to market a drug indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment, which became the first HER2-targeted ADC in China.

This approval makes brentuximab vedotin the second ADC approved for the Chinese market after Roche’s trastuzumab emtansine.

Market layout of Chinese ADCs

The FDA has so far approved a total of 6 ADCs. According to statistics, more than 60 ADC projects have entered the clinical studies worldwide, involving indications including urothelial carcinoma, triple-negative breast cancer, HER2-positive breast cancer, and glioblastoma, etc.

In the Chinese market, Pfizer has submitted a marketing application for inotuzumab ozogamicin, which is expected to be the third ADC to be marketed in China, in addition to the two drugs marketed. In the ADC R&D in China, over 10 Chinese pharmaceutical enterprises including Bio-Thera, Hengrui Medicine, Kelun Pharmaceutical, Zhejiang Medicine, Shanghai Pharma, and Fudan-Zhangjiang, etc. have got involved, with most of the ADCs in development targeting HER2 and indications including breast cancer, gastric cancer, non-small cell lung cancer, etc. Wherein, BAT8001 under Bio-Thera is fastest in the development progress; it is in phase III clinical trial, with the indication being HER2-positive advanced breast cancer; it is expected to be completed the clinical study final report and applied for an NDA in China in 2021.

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