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Sacituzumab Govitecan Receives Positive CHMP Opinion as a Second-Line Treatment for Metastatic Triple-Negative Breast Cancer in the EU

Oct 18, 2021 00:48 CST Updated 00:48
Gilead Sciences

Antiviral Drug Developer

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.


October 17, 2021 /BioonBIOON/ -- Gilead Sciences (Gilead) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of the targeted anti-cancer drug Trodelvy (sacituzumab govitecan-hziy) as a monotherapy for the treatment of patients who have previously received at least two therapies, including at least one therapyTreatment of Unresectable or Metastatic Triple-Negative Advanced DiseaseBreast Cancer(mTNBC) Adult Patients. Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which is expected to make a final decision later this year.

TNBC is the most aggressive subtype of breast cancer, accounting for approximately 15% of all breast cancer cases. It is more frequently observed in younger and premenopausal women and demonstrates a higher prevalence among Black and Hispanic women. The 5-year survival rate for this subtype is 12%, compared to 28% for other breast cancer subtypes. These poor prognoses are often accompanied by a significant decline in quality of life, particularly in recurrent or refractory disease.

Trodelvy is a novel first-in-class antibody-drug conjugate (ADC) targeting Trop-2, a cell surface protein expressed in TNBC and many otherTumoroverexpressed in.To date, Trodelvy has been approved in the United States, Switzerland, the United Kingdom, Australia, and Canada for the treatment of TNBC. Additionally, through its licensing partner Everest Medicines, Trodelvy is currently under regulatory review in China and Singapore.

It is worth mentioning that,Trodelvy is the first therapy to demonstrate superiority over standard of care in the treatment of metastatic TNBC, marking a significant advance in TNBC treatment.In the phase 3 ASCENT study, compared with chemotherapy, Trodelvy significantly prolonged progression-free survival (median PFS: 4.8 months vs. 1.7 months,Significantly reduces the risk of disease progression or death by 57%(HR=0.43, p<0.0001), regardless of brain metastasis status. Furthermore, compared with chemotherapy, Trodelvy significantly prolonged overall survival (median OS: 11.8 months vs. 6.9 months),Significantly reduces the risk of death by 49%（HR=0.51，p＜0.0001）。

Dr. Merdad Parsey, Chief Medical Officer of Gilead Sciences, stated: “Effective treatment options for patients with metastatic TNBC are highly limited, particularly following disease progression. We are very pleased with the CHMP’s positive opinion on Trodelvy, which brings us one step closer to making this much-needed therapy available to patients across Europe, and we look forward to the European Commission’s final decision. Trodelvy is the first targeted therapy to demonstrate superior overall survival compared to chemotherapy in the second-line treatment of metastatic TNBC, and it has the potential to become the new standard of care as a second-line treatment option.”

Trodelvy Structural Features (Image source: broadpharm.com)

Trodelvy is a novel, first-in-class antibody-drug conjugate (ADC) targeting Trop-2, consisting of a humanized IgG1 antibody targeting the TROP-2 antigen conjugated to SN-38, the active metabolite of the chemotherapeutic agent irinotecan (a topoisomerase I inhibitor), with a drug-to-antibody ratio of up to 7.6:1. Trop-2 is a ... in many epithelialTumora cell surface protein frequently expressed in various cancers (including TNBC), which is expressed in over 90% of TNBC cases. Trodelvy specifically binds to Trop-2 and delivers the anticancer agent SN-38 to kill cancer cells.

Trodelvy was developed by Immunomedics. At the core of its proprietary ADC platform is a novel linker that does not require enzymatic cleavage to release the payload, and can function within tumor cells andTumordelivering active drugs into the microenvironment, thereby inducing a bystander effect. In April 2019,Everest MedicinesSigned an agreement with Immunomedics to obtain the rights to Trodelvy in Greater China, South Korea, Mongolia, and Southeast Asian countries and regions. In September 2020, Gilead Sciences, Inc. acquired Immunomedics for $21 billion, adding Trodelvy to its portfolio.

In the United States, Trodelvy has been approved for two indications: (1) for the treatment of adult patients with unresectable locally advanced or metastatic TNBC who have received at least two prior therapies, at least one of which was for metastatic disease; (2) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

In China, Trodelvy (sacituzumab govitecan) was included in the 2020 edition of the *Chinese Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer* in October 2020., this guideline was formulated by the Breast Cancer Expert Committee of the National Cancer Quality Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Chinese Anti-Cancer Association# TumorJointly compiled by the Professional Committee on Clinical Drug Research. In May 2021, the National Medical Products Administration (NMPA) accepted the Biologics License Application (BLA) for Trodelvy and included it in the priority review program.

Breast cancer is the most common type of cancer among women, with over 2 million new cases diagnosed globally each year. Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases and is more prevalent in women under the age of 50 compared to other subtypes. TNBC specifically refers to breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is characterized by rapid progression, a very poor prognosis, and a 5-year survival rate of less than 15%. TNBC is unresponsive to both hormone therapy and HER2-targeted therapies (such as Roche’s Herceptin), leaving clinical treatment options highly limited and relying primarily on chemotherapy.

The CHMP's positive opinion and the regulatory approval of Trodelvy were based on the results of the Phase 3 ASCENT (NCT02574455) trial. This was an international, open-label Phase III study that enrolled over 500 patients with mTNBC who had previously received at least two prior therapies for metastatic disease. In the study, patients were randomized into two groups: one receiving Trodelvy and the other receiving physician's choice of chemotherapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), time to response, safety, and tolerability.

The results showed,The study met the primary and key secondary endpoints.: Compared with the chemotherapy group, the Trodelvy group demonstrated a statistically significant improvement in PFS (median PFS: 4.7 months vs. 1.7 months) and a 57% reduction in the risk of disease progression (HR=0.43, 95% CI: 0.35-0.54, p<0.0001). Additionally, the study met its key secondary endpoint: the Trodelvy group showed a statistically significant improvement in OS compared with the chemotherapy group (median OS: 11.8 months vs. 6.9 months) and a 49% reduction in the risk of death (HR=0.51; 95% CI: 0.41-0.62; p<0.0001). Furthermore, the ORR was significantly higher in the Trodelvy group compared with the chemotherapy group (35% vs. 5%). (Bioon.com)