Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1744 |
| INN | Zanidatamab |
| Status | Approved |
| Drug code(s) | ZW25 |
| Brand name | Ziihera® |
| mAb sequence source | mAb humanized |
| General Molecular Category | Bispecific, Biparatopic |
| Format, general category | Fragment-Fc |
| Format details | Fab-h-CH2-CH3 x scFv-h-CH2-CH3 |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | None |
| Target(s) | HER2, HER2 |
| Indications of clinical studies | Endometrial cancer, biliary tract cancer, breast cancer; HER2-positive metastatic gastric, gastroesophageal junction, and esophageal adenocarcinomas; ovarian cancer |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved US |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | September 15, 2016 |
| Start of Phase 2 | April 10, 2019 |
| Start of Phase 3 | December 01, 2021 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | 2024 |
| Date of first US approval | November 20, 2024 |
| INN, US product name | Zanidatamab, zanidatamab-hrii |
| US or EU approved indications | Treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test. |
| Company | Zymeworks |
| Licensee/Partner | BeiGene, Jazz Pharmaceuticals plc |
| Comments about company or candidate | Nov 20, 2024: Jazz Pharmaceuticals! The company announced the U.S. Food and Drug Administration granted accelerated approval of Ziihera® (zanidatamab-hrii) 50mg/mL for injection for intravenous use for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test. EMA starts MAA evaluation on June 20, 2024. June 10, 2024 -- Zymeworks Inc. announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China has accepted the BLA for zanidatamab for second-line treatment of HER2-positive BTC. PDUFA target action date of November 29, 2024; BLA has priority review. https://investor.jazzpharma.com/news-releases/news-release-details/zanidatamab-granted-priority-review-her2-positive-metastatic Jan 2024 press release: Key 2023 accomplishment - Jazz Pharmaceuticals, presented positive pivotal Phase 2b trial data (NCT04466891) evaluating zanidatamab in HER2-amplified BTC at the American Society of Clinical Oncology annual meeting and initiated rolling Biologics License Application (BLA) submission for accelerated approval in second-line BTC with completion expected in the first half of 2024. HERIZON-BTC-01 Phase 2 results published July 2023 (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00242-5/fulltext). Jazz seems likely to progress to Phase 3 in BTC; readout in GEA expected in 2024. According to Zymeworks pipeline HERIZON-BTC-01 phase 2 study for Biliary tract cancers (NCT04466891 HERIZON-BTC-01) is pivotal, and it is active non recruiting on clinicaltrials.gov as of March 31, 2023; Gastroesophageal adenocarcinoma cancer (NCT05152147 HERIZON-GEA-01) is recruiting as of April 5, 2023. There is also a phase 3 study for Biliary tract cancers NCT05615818, not yet recruiting as of March 15, 2023, but it is sponsored by UNICANCER and other hospitals, Oct. 19, 2022: Jazz Pharmaceuticals plc and Zymeworks Inc. announced that Jazz and Zymeworks' subsidiary, Zymeworks BC Inc., have entered into an exclusive licensing agreement under which Jazz will acquire development and commercialization rights to Zymeworks' zanidatamab across all indications in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks. Top-line clinical data for zanidatamab in biliary tract cancer (Phase 2 HERIZON-BTC-01 study) expected by end of 2022; potential to support first global regulatory filings. FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy, for first-line GEA. These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations from FDA for the treatment of biliary tract and gastric cancers, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer. NCT05152147 Phase 3 study in gastric and esophogeal cancer started in Dec 2021. Zymeworks Inc. announced that its partner, BeiGene, Ltd., has dosed the first patient in South Korea in a pivotal, single-arm clinical trial of zanidatamab (formerly ZW25) monotherapy in patients with advanced or metastatic HER2-amplified biliary tract cancer (BTC). Zymeworks will receive a US$10 million payment under its collaboration with BeiGene as a result of the achievement of this development milestone. Zymeworks and BeiGene are progressing the opening of multiple clinical trial sites in support of the global registration-enabling Phase 2b clinical trial of zanidatamab in patients with HER2-amplified BTC. In the Asia region, multiple sites are open for enrollment in South Korea, and in China all sites have been selected with enrollment anticipated to begin in the first quarter of 2021. This global zanidatamab study may enable the submission of a Biologics License Application by Zymeworks in the United States as early as 2022. Multiple clinical sites are now open to enrollment in the U.S., Europe, and Asia, with additional sites planned, including in Canada and South America. Nov 30, 2020: FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously-treated HER2 gene-amplified biliary tract cancer Nov 2020: Zymeworks Inc., a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, announced that the European Commission (EC) has granted Orphan Drug designation for zanidatamab, the company’s investigational HER2-targeted bispecific antibody, in patients with gastric cancer. July 2020: NCT04466891 registration-enabling Phase 2 study in 1L HER2+ biliary tract cancer started; company is planning for a potential BLA filing in 2022. Jan 2020: Zymeworks announced that ZW25 achieved two additional regulatory milestones, recently being granted Fast Track and Orphan Drug Designations by the FDA in refractory biliary tract cancer. NCT04224272 Phase 2 in breast cancer started in Jan 2020. May 2019: ZW 25 receives Fast track status from the US FDA for Gastroesophageal adenocarcinoma (First-line therapy, Combination therapy). April 15, 2019: Zymeworks Inc. today announced it has initiated its global multicenter Phase 2 (NCT03929666) clinical trial evaluating ZW25 in combination with standard of care chemotherapy for the first-line treatment of HER2-positive metastatic gastric, gastroesophageal junction, and esophageal adenocarcinomas. Nov 2018: BeiGene acquired exclusive development and commercial rights to Zymeworks’ bispecific candidates, ZW25 and ZW49, in Asia (excluding Japan), Australia, and New Zealand. The companies will collaborate on joint global development for selected indications. NCT02892123 Phase 1 study still recruiting as of Aug 2018. June 2017: In dose escalation portion of Phase 1 study, ZW25 was well-tolerated at all dose levels evaluated with single agent anti-tumor activity in patients with advanced HER2-expressing cancers that had progressed after multiple lines of therapy, including HER2-targeted agents. NCT02892123 Phase 1 recruiting as of Sep 2016; described as a humanized bispecific monoclonal antibody targeting the extracellular domain of HER2 in the clinicaltrials.gov record. US orphan drug designation for ovarian cancer. Orphan designation for ovarian cancer and gastric cancer, including cancer of the gastroesophageal junction. IND filed in July 2016. September 3, 2014 I CMC Biologics, Inc., a global leader in process development and contract manufacturing, and Zymeworks Inc., a Canadian biotherapeutics company and a world leader in the development of antibody therapeutics, have entered into a Master Services Agreement for process development, formulation development and cGMP clinical manufacturing of a recombinant human IgG1 bi-specific (heterodimeric) antibody. lead Azymetric™ oncology program and first therapeutic built on our proprietary ZymeCAD™ platform. |
| Full address of company | Vancouver, BC, Canada V5T 1G4 North America Canada https://www.zymeworks.com/contact/ |
IgG assembled from half-antibodies (Azymetrics); bispecific antibody that can simultaneously bind two non-overlapping epitopes, known as biparatopic binding, of HER2 resulting in dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and enhanced effector function. One binding site is scFv, other binding site is Fab
| Anticipated events | Regulatory review EU, China |
| Factor(s) contributing to discontinuation | None |