Jazz Pharmaceuticals plc has announced that the US Food and Drug Administration (FDA) has expedited the approval of Ziihera (zanidatamab-hrii) 50mg/mL for intravenous administration. This approval targets adults with previously treated, unresectable, or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as identified through an FDA-endorsed test. The expedited approval is predicated on a 52% objective response rate (ORR) and a median response duration of 14.9 months as evaluated by independent central review (ICR). The ongoing approval for this usage may require validation and elaboration of clinical benefit in a confirmatory trial. The ongoing HERIZON-BTC-302 phase 3 trial is designed to assess zanidatamab together with standard treatment against standard treatment alone for first-line HER2-positive BTC patients.
“BTC is a brutal disease with a grim prognosis and a five-year survival rate below five percent for metastatic instances. Patients with unresectable or metastatic HER2-positive BTC have been in dire need of viable treatments, with scarce sanctioned options,” expressed Rob Iannone, M.D., M.S.C.E., executive vice president and global research head at Jazz Pharmaceuticals. “The authorization of Ziihera, which earlier obtained the FDA’s Breakthrough Therapy Designation for this indication, signifies a meaningful progress and introduces the inaugural and exclusive dual HER2-focused bispecific antibody treatment devoid of chemotherapy for BTC patients. We are committed to further researching zanidatamab for BTC and other HER2-expressing solid tumors, aiming to improve results for more individuals battling these challenging HER2-positive cancers.”
The FDA’s decision to approve Ziihera relies on robust data from the HERIZON-BTC-01 trial, where zanidatamab was examined as a single agent for pre-treated HER2-positive BTC patients. This study stands as the largest of its kind in a phase 2b clinical trial for this patient category. It reached its primary endpoint of confirmed objective response rate (cORR) per independent central review (ICR), with outcomes featured at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023 and published in The Lancet Oncology. The extended follow-up data, which showed advancements over previously reported DOR, were shared at ASCO Annual Meeting 2024.
“As an oncologist and clinical researcher focusing on improving care for biliary tract and liver cancer patients, I’ve observed the critical need for effective treatments for these conditions,” noted Dr. James Harding from Memorial Sloan Kettering Cancer Center. “Zanidatamab has shown antitumor efficacy and represents a new alternative for HER2-positive biliary tract cancer patients. I am eager to witness further successful drug development for biliary tract cancer patients.”
“Metastatic BTC imposes a heavy burden on patients and their families, affecting their emotional and mental health, ” remarked Stacie Lindsey, Cholangiocarcinoma Foundation CEO and founder. “Ziihera’s approval brings hope, offering patients and their loved ones a chance for more time and a better quality of life, priceless to the BTC community.”
Ziihera’s effectiveness was tested in 62 HER2-positive BTC patients in HERIZON-BTC-01’s Cohort 1, with crucial efficacy measures focusing on ORR and DOR as determined by ICR using RECIST v1.1. The study reported a 52% ORR with a Kaplan Meier (KM) estimated median DOR of 14.9 months.
The phase 2b HERIZON-BTC-01 study was an open-label, global phase 2b study with 87 HER2-amplified BTC patients enrolled across two cohorts, including 62 patients with HER2 IHC 3+ BTC. The primary goal was ORR by independent central review (ICR) in Cohort 1, with secondary objectives covering additional safety and efficacy outcomes.
Ziihera (zanidatamab-hrii), a bispecific HER2-targeted antibody, binds to two extracellular HER2 sites. Its binding leads to internalization and receptor reduction on tumor cell surfaces, inducing complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and cellular phagocytosis, resulting in tumor growth inhibition and cell death.
Zanidatamab is not sanctioned outside the United States but is undergoing development in several clinical trials for patients with solid tumors expressing HER2, collaboratively by Jazz and BeiGene, Ltd. under license from Zymeworks, which originally developed the molecule.
The FDA awarded Breakthrough Therapy designation to zanidatamab for previously treated HER2 gene-amplified BTC and two Fast Track designations for use as a single agent for resistant BTC and combined with standard chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab received Orphan Drug designations from the FDA and European Medicines Agency for BTC, GEA, and gastric cancer treatment.
Biliary Tract Cancer (BTC), including gallbladder cancer and cholangiocarcinoma, are amongst the rarest adult cancers globally, often linked to dismal prognoses. HER2, a validated target for antitumor treatment in various cancers, is involved in approximately 12,000 HER2+ BTC diagnoses annually across the US, Europe, and Japan.
Jazz Pharmaceuticals plc is a worldwide biopharma enterprise dedicated to innovative transformation of patient and family lives by developing life-altering treatments for serious illnesses with limited or absent therapeutic possibilities.