A few days ago, Gilead ADC drug Trodelvy has received positive opinions from the European Medicines Agency (EMA) Committee on Medicinal Products for Human Use (CHMP) for monotherapy in adult patients with unresectable or metastatic triple-negative breast cancer (TNBC). Gilead expects that the European Union will make a final regulatory decision on the treatment of TNBC later this year.

This time Trodelvy received positive opinions from the European Union, mainly based on the positive results of the Phase 3 ASCENT trial. In the previous phase 3 ASCENT study, compared with chemotherapy, Gilead Trodelvy treatment can significantly prolong the PFS of patients by 3.1 months, significantly reduce the risk of disease progression or death by 57%, and significantly extend the patient’s OS by 3.9 months. The risk of death can also be significantly reduced by 49%. It is worth mentioning that Gilead Trodelvy is also the first therapy to improve the progression-free survival (PFS) and overall survival (OS) of patients with metastatic triple-negative breast cancer.

Just 5 months ago, the FDA approved Gilead Trodelvy for the same indication in April, and the drug is currently on the market in the UK, Australia, Switzerland and Canada. Merdad Parsey, chief marketing officer of Gilead, said that for patients with metastatic triple-negative breast cancer, currently clinically effective treatment options are extremely limited, especially once their condition begins to progress. Metastatic triple-negative breast cancer is ineffective against hormone therapy and HER2 targeted therapy (such as Herceptin Roche), and clinical treatment options are very limited, mainly relying on chemotherapy. This is good news for European patients with breast cancer, and triple-negative breast cancer is the most aggressive form of the disease, and is more commonly diagnosed in young and premenopausal women, and in black and Hispanic women Chinese are also more common. The prognosis of this disease is also poor, with a five-year survival rate of 12%, compared with 28% for other breast cancer types.

Trodelvy was originally developed by Immunomedics. In April 2019, Everest Medicines and Immunomedics signed a cooperation agreement to obtain Trodelvy's rights in Greater China, South Korea, Mongolia, Southeast Asia and other countries and regions. In September 2020, Gilead acquired Immunomedics for US$21 billion and included Trodelvy in the bag. The drug is currently under review in mainland China.

Trodelvy is a new and pioneering antibody-conjugated drug (ADC) targeting Trop-2. It consists of a humanized IgG1 antibody targeting Trop-2 antigen and a chemotherapeutic drug irinotecan (a topoisomerase I inhibitor). SN-38, a metabolically active product of drug), is coupled with a drug-antibody ratio of up to 7.6:1. Trop-2 expressed in more than 90% of TNBC is a cell surface protein. Trodelvy targets to bind to Trop-2 and delivers the anti-cancer agent SN-38 to kill cancer cells.

In addition, Gilead’s development plan for Trodelvy also includes the exploration of multiple other solid tumor indications, such as other types of metastatic triple-negative breast cancer and metastatic urothelial cancer, hormone receptor positive/human epidermal growth Factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. In order to qualify for the treatment of Gilead Trodelvy, EU patients must have received two or more previous systemic treatments, at least one of which is used to treat disease progression.

In terms of competitors, in March 2019, the U.S. Food and Drug Administration (FDA) approved Roche’s PD-L1 tumor immunotherapy Tecentriq combined with chemotherapy Abraxane for the first-line treatment of PD-L1-positive locally advanced or metastatic triple-negative breast cancer patients . This approval makes the combination of Tecentriq and Abraxane the first cancer immunotherapy regimen for the treatment of TNBC. In November 2020, the US FDA again approved Merck's Keytruda combined with chemotherapy to treat patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1. This is also the first approval of Keytruda in the field of breast cancer.