CHMP Endorses Jazz Pharma's Zanidatamab for Advanced HER2-Positive Biliary Tract Cancer

DUBLIN, April 25, 2025 – Jazz Pharmaceuticals plc, a prominent name in the biopharmaceutical sector, has garnered significant attention with the recent announcement from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The CHMP has issued a favorable verdict on the conditional marketing approval of zanidatamab. This investigational therapy, targeting human epidermal growth factor receptor 2 (HER2), is a bispecific antibody designed to treat adults contending with unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) who have undergone prior systemic therapy.

Biliary tract cancers, encompassing gallbladder cancer and cholangiocarcinoma, are relatively rare, representing less than 1% of all human cancers. Despite their rarity, the prognosis for such cancers is often grim due to late-stage diagnosis attributed to non-specific early symptoms. The necessity for new treatment options is evident, with HER2-positive BTC being particularly aggressive and lacking specialized therapies within the European Union.

The positive CHMP opinion marks a critical advancement for both physicians and patients facing HER2-positive BTCs—a group of cancers noted for their aggressive nature and limited treatment pathways. Robert Iannone, MD, M.S.C.E., who holds the position of executive vice president and global head of research and development at Jazz Pharmaceuticals, emphasized the potential impact of this development. He noted that, if approved, zanidatamab would become the first HER2-specific therapy available for this challenging form of cancer in Europe.

This recommendation is founded on findings from the Phase 2b HERIZON-BTC-01 trial, which focused on the efficacy of zanidatamab in patients with previously treated, advanced or metastatic HER2-positive BTC. Data indicated promising outcomes, offering hope for more effective management of this cancer type. HER2 overexpression has been recognized as a distinct molecular subtype of BTC, associated with poorer outcomes compared to HER2-negative cases.

The European Commission is now tasked with reviewing the CHMP's recommendation. A nod from the Commission would allow the approval of zanidatamab across all EU Member States, as well as Iceland, Norway, and Liechtenstein.

Zanidatamab operates by simultaneously binding to two extracellular domains of HER2 on separate monomers, leading to the internalization and reduction of the receptor on the cell surface. This binding action triggers cytotoxic effects that inhibit tumor growth and facilitate cancer cell death.

In the United States, the FDA granted accelerated approval to zanidatamab-hrii (marketed as Ziihera®) in late 2024 for adults with previously treated, inoperable, or metastatic HER2-positive BTC, based on specific response metrics. This approval is conditional on further validation of its benefits through ongoing clinical trials, particularly the Phase 3 HERIZON-BTC-302 trial.

Jazz Pharmaceuticals, alongside BeiGene, is actively conducting multiple clinical trials to explore zanidatamab's potential as a targeted treatment for various solid tumors expressing HER2. The collaboration between these companies, underpinned by licensing agreements with Zymeworks—who initially developed zanidatamab—illustrates a concerted effort to broaden the scope of possible treatments for HER2-positive cancers.

As anticipation builds for the European Commission’s decision, the potential approval of zanidatamab represents not just a significant milestone for Jazz Pharmaceuticals but a beacon of hope for patients who face limited therapeutic options against a formidable cancer type.