Jazz Pharmaceuticals Launches Ziihera After FDA Nod in HER2-Positive GEA

Jazz Pharmaceuticals launched Ziihera in the U.S. after FDA approval for first-line treatment of eligible HER2-positive, unresectable or metastatic gastroesophageal adenocarcinoma. The drug may be used with tislelizumab and chemotherapy, or with chemotherapy alone for certain HER2 IHC 3+ patients. In the Phase III HERIZON-GEA-01 trial, Ziihera-based regimens reduced the risk of disease progression or death by 35%; the triplet regimen also extended median overall survival to 26.4 months, a 28% reduction in the risk of death versus trastuzumab. Jazz estimates the U.S. addressable market at 3,000–4,000 patients annually and raised Ziihera’s peak sales outlook to $3 billion–$5 billion. The company plans to leverage its existing commercial infrastructure while pursuing additional cancer indications and international regulatory filings. 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. Rob Iannone, Jazz’s global head of R&D and chief medical officer, said the FDA-approved label was supported by results from the Phase III HERIZON-GEA-01 trial. Both Ziihera-containing treatment arms showed statistically significant progression-free survival improvements, with median progression-free survival exceeding 12 months and a 35% reduction in the risk of progression or death versus a trastuzumab control arm, according to the company. 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. 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.