The FDA grants Breakthrough Therapy designation to new medicines that are intended to treat a serious condition and where clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint. Zanidatamab will now be eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program.
“This Breakthrough Therapy designation from the FDA, based on data generated in BTC patients treated in the initial Phase 1 trial, is recognition of the potential of zanidatamab to provide a new approach to cancer treatment,” said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. “This milestone supports our strategy for accelerated approval and will help make zanidatamab available for patients as quickly as possible.”
“BTC is a rare and aggressive cancer,” said James Priour, Senior Vice President, Commercial, at Zymeworks. “Receiving this designation from the FDA is testament to the potential of zanidatamab to be the first HER2-targeting therapy approved for metastatic BTC patients.”
Earlier this year, Zymeworks initiated a global Phase 2b registration-enabling study of single agent zanidatamab in patients with previously treated HER2 gene-amplified BTC. This study, which is currently enrolling patients, is designed to support accelerated approval based on a primary endpoint of objective response rate, and secondary endpoints of duration of response and safety and may enable submission of a Biologics License Application (BLA) as early as 2022.
This Breakthrough Therapy designation was based on an ongoing clinical trial of zanidatamab in patients with locally advanced (unresectable) and/or metastatic HER2-expressing tumors including BTC. Updated clinical data for single agent zanidatamab patients with BTC has been accepted for presentation at the upcoming American Society of Clinical Oncology’s Virtual Gastrointestinal Cancers Symposium (ASCO GI) January 15-17, 2021.
Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients.
Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and registration-enabling clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. In addition to Breakthrough Therapy designation for zanidatamab in BTC, the U.S. FDA has granted two Fast Track designations to zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy, for first-line gastroesophageal adenocarcinoma (GEA). Zanidatamab has also received Orphan Drug designations for the treatment of biliary tract, gastric and ovarian cancers from the U.S. FDA, as well as Orphan Drug designation for the treatment of gastric cancer from the European Medicines Agency.
Biliary tract cancer (BTC), including gallbladder cancer and cholangiocarcinoma (bile duct cancer), accounts for approximately 3% of all adult cancers and is associated with a poor prognosis. Globally, more than 210,000 people are diagnosed with BTC every year. Most patients (> 65%) with BTC are diagnosed with tumors that cannot be removed surgically, and even those patients who undergo potentially curative surgery have a high recurrence rate. Treatment options are limited for patients with advanced BTC who experience disease progression after front-line chemotherapy.
The human epidermal growth factor receptor 2 (HER2) is a well-described target for anti-cancer therapy. Tumor cells that produce a higher than normal level of HER2 tend to grow more quickly and spread to other parts of the body. About 5% to 19% of patients with BTC have tumors that express HER2, suggesting that these patients may potentially benefit from HER2-targeted therapy. Currently no HER2-targeted therapy has been approved for the treatment of BTC.
Source: Company Press Release