Jazz Pharmaceuticals (NASDAQ:JAZZ) outlined its plans for the U.S. launch of Ziihera following FDA approval of the therapy for first-line HER2-positive unresectable, locally advanced or metastatic gastroesophageal adenocarcinoma, or GEA.
Ziihera, or zanidatamab, is approved in combination with tislelizumab and fluoropyrimidine- and platinum-containing chemotherapy for patients whose tumors are HER2 IHC 3+ or IHC 2+ and ISH-positive, regardless of PD-L1 status. It is also approved with chemotherapy alone for patients with HER2 IHC 3+ disease.
The triplet regimen of Ziihera, tislelizumab and chemotherapy produced median overall survival of 26.4 months, representing more than seven months of improvement and a 28% reduction in the risk of death compared with trastuzumab, Iannone said. Jazz also said nearly 40% of patients receiving the triplet were estimated to be alive after three years.
Label, dosing and safety
Ziihera is administered intravenously with chemotherapy, with or without tislelizumab. Patients weighing less than 70 kilograms may receive 1,800 milligrams every three weeks or 1,200 milligrams every two weeks, while patients weighing 70 kilograms or more may receive 2,400 milligrams every three weeks or 1,600 milligrams every two weeks.
The company highlighted that every-two-week dosing can align with FOLFOX chemotherapy administration. HERIZON-GEA-01 primarily used CAPOX chemotherapy, but Jazz said FOLFOX is more widely used in the United States.
The label carries boxed warnings for diarrhea and embryo-fetal toxicity. Physicians are advised to prescribe antidiarrheal prophylaxis during the first treatment cycle when Ziihera is used with fluoropyrimidine- and platinum-containing chemotherapy. Iannone said treatment-related diarrhea leading to Ziihera discontinuation occurred in less than 5% of patients across the trial’s experimental arms.
Other warnings include left ventricular dysfunction and infusion-related reactions. The most common adverse reactions reported with the triplet included diarrhea, nausea, decreased appetite, hypokalemia, vomiting, fatigue, peripheral neuropathy, rash and infusion-related reactions.
Commercial launch targets defined patient population
Chumi Khurana, Jazz’s head of oncology franchise, said GEA includes cancers of the stomach, gastroesophageal junction and esophagus. About 20% of GEA patients are diagnosed with HER2-positive disease, equating to approximately 8,000 annual cases in the U.S., according to the company.
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, although the rate of HER2-positive patients who subsequently receive HER2-targeted therapy ranges from 60% to 80%, depending on treatment setting.
Jazz expects its existing commercial infrastructure in biliary tract cancer, or BTC, to support the GEA launch. The company cited more than 90% overlap between its BTC and GEA target accounts and said it does not expect to need a major commercial expansion. About 70% of GEA treatment occurs in community settings and 30% in academic centers, Khurana said.
The company plans to use nurse educators, peer-to-peer education, patient starter kits and its JazzCares support program to help providers initiate treatment and manage adverse events. Jazz also said Ziihera can be ordered using its existing permanent J-code.
Expanded sales outlook and development plans
Sam Pearce, Jazz’s chief commercial officer, said the company increased its estimate of Ziihera peak sales potential to $3 billion to $5 billion, from a previous estimate of more than $2 billion. Jazz did not provide a sales breakdown by indication but said BTC and GEA are significant contributors to the revised estimate.
The company is also advancing zanidatamab in other HER2-expressing cancers, including breast cancer, colorectal cancer and non-small cell lung cancer. Pearce said top-line data from the EmpowHER-303 breast cancer trial are expected in late 2027 or early 2028. Jazz is also studying the drug in earlier-stage breast cancer, front-line BTC and a pan-tumor program.
Jazz expects to submit Ziihera for European regulatory review by the end of the year and said filings have also been made in the U.K. and Canada through Project Orbis.
About Jazz Pharmaceuticals (NASDAQ:JAZZ)
Jazz Pharmaceuticals plc is a global biopharmaceutical company focused on developing and commercializing therapies in neuroscience and oncology. The company’s research and development efforts target unmet medical needs in sleep disorders, hematologic malignancies, rare neurological conditions and solid tumors. Jazz’s product portfolio includes therapies for narcolepsy, hepatic veno-occlusive disease, acute myeloid leukemia and other serious disorders.
Flagship products from Jazz Pharmaceuticals include Xyrem® (sodium oxybate) and Xywav® (calcium, magnesium, potassium, and sodium oxybates) for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy.
