Star ADC Drug DS-8201 Set to Enter China as Over a Dozen New ADCs Queue Up, Poised to Reshape Breast Cancer Treatment Landscape

Recently, the official website of the Center for Drug Evaluation of the National Medical Products Administration announced that the marketing application of DS-8201, a HER2-targeted antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and AstraZeneca, has been included in the priority review. The proposed indication is monotherapy for unresectable or metastatic HER2-positive breast cancer in patients who have previously received one or more anti-HER2 treatments. If this drug is successfully marketed, it will add a powerful option to the clinical treatment of advanced breast cancer in China.

Source: CDE Official Website

People who play MOBA games know that ADC is the core position in the team with the highest output, and ADC drugs in cancer treatment can play a similar role.

Antibody-drug conjugates (ADCs) consist of three components: monoclonal antibodies that specifically recognize the target antigen, small-molecule cytotoxic drugs responsible for effective killing, and linkers that connect the antibody with the cytotoxic drug. Compared to traditional chemotherapy and targeted therapy drugs, the design concept of ADC drugs is quite artistic. Ideally, due to their precise targeting recognition sites, they can avoid the high toxic side effects of traditional chemotherapy while effectively eradicating dormant cancer cells. In addition to their targeted effect, ADC drugs can also exert a bystander effect to further damage tumor tissues.

The Superstar in ADC —— DS-8201

DS-8201, marketed under the brand name Enhertu, targets HER2 as indicated by its name. Its linker is a cleavable linker, and the cytotoxic drug it delivers is a topoisomerase I inhibitor. DS-8201 received approval for breast cancer indication in December 2019, for treating patients with HER2-positive unresectable or metastatic breast cancer who have undergone third-line treatment. Based on the latest results from DESTINY-Breast03, the 2022 V1 edition of the NCCN guidelines has listed DS-8201 as the preferred regimen for second-line treatment of HER2-positive, recurrent unresectable, or stage IV breast cancer.

In addition, DS-8201 has also been approved for the indication of locally advanced or metastatic HER2-positive gastric or gastroesophageal adenocarcinoma and received Breakthrough Therapy Designation for patients with HER2-mutant metastatic non-small cell lung cancer whose disease has progressed during or after platinum-based chemotherapy. It has also shown promising clinical trial data in treating HER2-positive colorectal cancer, making it truly a "multi-faceted cancer fighter."

Notably, in the pivotal Phase III clinical trial of DS-8201 for the treatment of patients with unresectable or metastatic breast cancer exhibiting low HER2 expression, DS-8201 significantly prolonged progression-free survival and overall survival compared to chemotherapy. The results of this trial are expected to transform the treatment landscape for HER2-low breast cancer.

The basic information of ADC drugs approved by the US FDA and the EU EMA for breast cancer treatment is shown in Table 1.

Table 1: Basic Information on ADCs in the Field of Breast Cancer Treatment Already Marketed Overseas

More Than Ten New ADC Drugs in the Pipeline: Will the Breast Cancer Treatment Landscape Change?

In recent years, the competition in the ADC development track in China has reached a fever pitch. According to data from the CDE's official website, as of April 2022, there were already 15 ADCs under development for the breast cancer indication. Representative products that are either marketed or under development are shown in Table 2.

Table 2 Representative Anti-Breast Cancer ADCs Marketed/Under Development in China

We can see that currently, for the indication of breast cancer, the targets of ADCs under research are mainly concentrated on HER2 and TROP2. With the opportunity of DS-8201 receiving priority review, it is hoped that more ADC drugs will enter the market in the future.

Editor: Liuli

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