Jazz Pharmaceuticals Launches Ziihera in U.S. After FDA Approval for HER2-Positive GEA
Jazz Pharmaceuticals has begun the U.S. launch of Ziihera (zanidatamab) after the FDA approved the therapy for certain patients with previously untreated HER2-positive gastroesophageal adenocarcinoma (GEA). The indication covers unresectable, locally advanced or metastatic disease.
The approval covers Ziihera in combination with tislelizumab, a PD-1 inhibitor, plus fluoropyrimidine- and platinum-containing chemotherapy for tumors that are HER2 IHC 3+ or IHC 2+ and ISH-positive, irrespective of PD-L1 status. Ziihera is also approved with chemotherapy alone for patients with HER2 IHC 3+ tumors.
Rob Iannone, Jazz's global head of R&D and chief medical officer, said the label is supported by the Phase III HERIZON-GEA-01 trial. In both Ziihera-containing treatment arms, progression-free survival showed a statistically significant improvement, with median PFS exceeding 12 months and a 35% lower risk of progression or death compared with a trastuzumab-based control arm.
In the triplet combination of Ziihera, tislelizumab and chemotherapy, median overall survival reached 26.4 months—more than a seven-month improvement over trastuzumab—and the regimen was associated with a 28% reduction in the risk of death. Jazz said nearly 40% of patients who received the triplet were alive at three years.
The approval marks a meaningful step for Jazz as it works to expand its oncology franchise beyond established neuroscience and rare-disease products. Zanidatamab is a bispecific antibody that binds two HER2 epitopes, and the new data suggest the molecule can be paired effectively with PD-1 blockade and chemotherapy in a first-line gastroesophageal setting. The launch also gives U.S. oncologists an alternative to trastuzumab-based regimens, which have been the standard HER2-targeted backbone in this disease for years.
Ziihera is given intravenously with chemotherapy, with or without tislelizumab. Patients weighing less than 70 kg may receive 1,800 mg every three weeks or 1,200 mg every two weeks, while patients weighing 70 kg or more may receive 2,400 mg every three weeks or 1,600 mg every two weeks. Jazz noted that the every-two-week schedule can be aligned with FOLFOX chemotherapy, which is more widely used in the U.S. than the CAPOX regimen primarily used in the HERIZON-GEA-01 trial.
The label includes boxed warnings for diarrhea and embryo-fetal toxicity. Jazz advised that antidiarrheal prophylaxis be prescribed during the first treatment cycle when Ziihera is used with fluoropyrimidine- and platinum-containing chemotherapy. Iannone said treatment-related diarrhea leading to discontinuation of Ziihera occurred in less than 5% of patients in the trial's experimental arms. Other warnings cover left ventricular dysfunction and infusion-related reactions. The most common adverse events in the triplet arm included diarrhea, nausea, decreased appetite, hypokalemia, vomiting, fatigue, peripheral neuropathy, rash and infusion-related reactions.
Chumi Khurana, Jazz's head of oncology franchise, said GEA includes cancers of the stomach, gastroesophageal junction and esophagus. About 20% of patients with GEA are HER2-positive, representing roughly 8,000 U.S. cases each year. After accounting for unresectable disease, first-line treatment eligibility and HER2 testing, Jazz estimates an annual addressable U.S. population of approximately 3,000 to 4,000 patients.
Khurana said 80% to 90% of patients undergo biomarker testing at diagnosis, but the share of HER2-positive patients who actually receive HER2-targeted therapy ranges from 60% to 80% depending on the treatment setting. That gap in targeted therapy use is one reason Jazz sees room to grow in the community oncology channel, where about 70% of GEA cases are treated. The remaining 30% are managed at academic centers.
Jazz expects its existing biliary tract cancer (BTC) commercial infrastructure to support the GEA launch. The company said more than 90% of its BTC and GEA target accounts overlap and that it does not anticipate a large commercial expansion. Launch support will include nurse educators, peer-to-peer education, patient starter kits and the JazzCares program. Ziihera can be ordered using the company's existing permanent J-code.
Sam Pearce, Jazz's chief commercial officer, said the company now believes Ziihera can reach $3 billion to $5 billion in peak sales, up from a prior estimate of more than $2 billion. Jazz did not break down the forecast by indication but said BTC and GEA both contribute meaningfully to the revised view.
Beyond GEA, Jazz is evaluating zanidatamab in other HER2-expressing tumor types, including breast cancer, colorectal cancer and non-small cell lung cancer. Top-line data from the EmpowHER-303 breast cancer trial are expected in late 2027 or early 2028. The company is also studying the drug in earlier-stage breast cancer, front-line BTC and a pan-tumor program.
Jazz plans to submit Ziihera for European regulatory review by the end of the year and has filed in the U.K. and Canada through Project Orbis.
Jazz Pharmaceuticals is a global biopharmaceutical company with a focus on neuroscience and oncology. Its portfolio includes therapies for narcolepsy, hepatic veno-occlusive disease, acute myeloid leukemia and other serious conditions. The company's established neuroscience brands include Xyrem and Xywav, while Ziihera represents one of the key growth assets in its oncology pipeline.