China-based Everest Medicines, a biopharmaceutical company focused on developing and commercializing transformative products, address critical unmet medical needs for patients in Greater China and other parts of Asia, has received approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the People’s Republic of China to start enrolling patients in registration clinical study of sacituzumab govitecan, also known as IMMU132.

Sacituzumab govitecan is an antibody-drug conjugate (ADC) that links SN-38, the active metabolite of irinotecan, via a hydrolyzable linker to a humanized monoclonal antibody against the human trophoblast cell-surface antigen 2 (Trop-2). Trop-2 is a membrane antigen that is frequently over-expressed in many common epithelial cancers. Sacituzumab govitecan delivers high concentrations of the SN-38 payload to tumors. Sacituzumab govitecan has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration and its BLA is under FDA review as a treatment for patients with metastatic triple-negative breast cancer in the later-line setting.

Immunomedics, Everest Medicines‘ partner, was been granted breakthrough therapy designation for sacituzumab govitecan by the US FDA and submitted their BLA for 3rd line metastatic triple-negative breast cancer (mTNBC) in December 2019. The IND for sacituzumab govitecan in China was accepted by the NMPA in December 2019.

MabPlex
 

Registration trial: mTNBC
Following the approval of the Clinical Trial Application (CTA) in China, Everest Medicines plans to initiate a pivotal Phase III clinical trial of sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

Metastatic triple-negative breast cancer is a highly aggressive disease and accounts for approximately 15% of all breast cancer types worldwide. [1][2][3]

The median age of breast cancer diagnoses tends to be younger in China than in western countries, and the percentage of TNBC molecular subtype has increased to 20.3% in the past 10 years. TNBC cells lack sufficient estrogen, progesterone, or HER2 receptor expression to benefit from the use of hormonal or HER2-directed therapy. Overall survival among patients with this form of breast cancer has not changed in the past 20 years, which highlights the need for advances in therapeutic options for these patients. [4][5][6][7][8]

First-in-class
Sacituzumab govitecan is a novel, potential first-in-class antibody-drug conjugate targeting the Trop-2 receptor expressed by many solid cancers and delivering the moderately-toxic drug, SN-38, directly to the tumor and the tumor microenvironment.

The FDA previously granted Fast Track Designation and Breakthrough Therapy Designation to sacituzumab govitecan for the treatment of patients with mTNBC who have received prior therapies for metastatic disease.

The FDA is currently reviewing a biologics license application for the therapeutic candidate submitted by Immunomedics for later-line mTNBC.

“Metastatic triple-negative breast cancer is a devastating disease with limited therapeutic options and an overall survival rate that has remained unchanged for two decades,” said Yang Shi, M.D., Chief Medical Officer for Oncology and Immunology at Everest Medicines.

“We are pleased to receive CTA approval of sacituzumab govitecan, which represents an opportunity to advance a potential novel treatment option for patients in China.”

Licensing agreement
Under a licensing agreement with Immunomedics, Everest Medicines has exclusive rights to develop, register, and commercialize sacituzumab govitecan for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries.

“Everest is excited to advance the development of this important medicine for patients. The speed at which this regulatory milestone was achieved is a testament to our team’s leadership and commitment to bring the latest therapeutic innovations to people in Greater China in disease areas with an urgent medical need,” said Kerry Blanchard, MD, Ph.D., Chief Executive Officer of Everest Medicines.

“We look forward to realizing the full potential of sacituzumab govitecan and its novel mechanism of action across other important cancer indications in China and other Asia geographies,” Blanchard further noted.

Collaboration and Investment
In March 2020 Everest Medicines established a global manufacturing site in Jiashan National Economic and Technological Development Zone with a U.S. $100 million investment from Jiashan SDIC to support Everest’s drug development facilities in China to support several clinical trials for registration and to build good manufacturing practice (GMP) manufacturing and good storage practice (GSP) facilities in the Jiashan National Economic and Technological Development Zone.

Under the terms of the agreement, Everest Medicines, start building build manufacturing capabilities in 2020 that comply with US Food and Drug Administration and European Medicines Agency standards to meet both demands in Asia and in the global market.

Jiashan is a county in Zhejiang Province that borders Shanghai and allows easy access to downtown Shanghai.

“This partnership with Jiashan will help Everest Medicines meet the growing demand for innovative medicines in China and Asia,” noted Neo Zhang, Chief Operations Officer of Everest Medicines.

“In 2018 the Integrated Development of Yangtze River Delta was highlighted as one of China’s national strategies designed to foster the development of a number of world-class industrial clusters and build the area into a key national innovation hub by 2025,” Neo Zhang said

“Jiashan is at the forefront of this integration and has established itself as an innovation-driven industrial ecosystem where Everest Medicines can enjoy efficient local manufacturing and research and development. The close proximity to Shanghai is also a great advantage in terms of attracting talent,” Neo Zhang added.

“Innovative medicines are rapidly becoming a mainstay of Chinese and Asian healthcare. We have built a solid foundation for the development and commercialization of our innovative medicines. The establishment of our China holding company in Jiashan strengthens Everest Medicines by providing us the opportunity to manufacture world-class medicines in China,” concluded Everest Medicines’ Blanchard.

Reference
[1] DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin 2016;66:31-42.
[2] Plasilova ML, Hayse B, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR. Features of triple-negative breast cancer: analysis of 38,813 cases from the National Cancer Database. Medicine (Baltimore) 2016;95(35):e4614.
[3] Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ ethnicity, poverty, and state. J Natl Cancer Inst 2015;107(6):djv048.
[4] Khosravi-Shahi P, Cabezón-Gutiérrez L, Custodio-Cabello S. Metastatic triple-negative breast cancer: optimizing treatment options, new and emerging targeted therapies. Asia Pac J Clin Oncol 2018;14: 32-9.
[5] Brufsky A, Valero V, Tiangco B, et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat 2012;133: 1067-75.
[6] Perez EA, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2- negative (triple negative) breast cancer. Breast Cancer Res Treat 2010;121:261-71.
[7] Park IH, Im SA, Jung KH, et al. Randomized open-label phase III trial of irinotecan plus capecitabine versus capecitabine monotherapy in patients with metastatic breast cancer previously treated with anthracycline and taxane: PROCEED trial (KCSG BR 11-01). Cancer Res Treat 2019; 51:43-52.
[8] Twelves C, Awada A, Cortes J, et al. Subgroup analyses from a phase 3, open-label, randomized study of eribulin mesylate versus capecitabine in pretreated patients with advanced or metastatic breast cancer. Breast Cancer (Auckl) 2016;10:77- 84