U.S. FDA Approves Ziihera® (zanidatamab-hrii) with and without Tislelizumab plus Chemotherapy in First-Line HER2+ Advanced Gastroesophageal Adenocarcinoma

Rhea-AI Summary

Jazz Pharmaceuticals (Nasdaq:JAZZ) announced U.S. FDA approval of two Ziihera (zanidatamab-hrii) regimens for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (GEA). One regimen combines Ziihera with Tevimbra (tislelizumab) plus fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+); the other combines Ziihera with chemotherapy alone (HER2+ IHC 3+).

According to Jazz, Phase 3 HERIZON-GEA-01 data showed median progression-free survival of 12.4 months versus 8.1 months and median overall survival of 26.4 versus 19.2 months versus trastuzumab plus chemotherapy, with risk reductions of 35% for progression or death and 28% for death. Ziihera regimens carry boxed warnings for severe diarrhea and embryo-fetal toxicity, and additional risks including left ventricular dysfunction and infusion-related reactions. Jazz will host an investor webcast on August 25, 2026, at 4:30 p.m. ET to discuss the approval and the zanidatamab program.

Positive

• FDA approved two Ziihera-based first-line regimens for HER2+ unresectable locally advanced or metastatic GEA
• Regimen with tislelizumab and chemotherapy covers HER2+ IHC 3+ and IHC 2+/ISH+ patients regardless of PD-L1 status
• Median overall survival 26.4 vs 19.2 months; 28% reduction in risk of death vs trastuzumab plus chemotherapy
• Median progression-free survival 12.4 vs 8.1 months; 35% reduction in risk of progression or death
• PFS and OS benefits were generally consistent across major prespecified subgroups, including geographic region and PD-L1 status
• Ziihera is already approved in the U.S. for HER2+ biliary tract cancer and in the EU and other countries, expanding its commercial footprint

Negative

• Ziihera prescribing information carries boxed warnings for severe diarrhea and embryo-fetal toxicity
• In combo with chemotherapy and tislelizumab, diarrhea occurred in 85% of patients; 24% Grade 3, 2.1% Grade 4, with 1.5% fatal cases
• In combo with chemotherapy alone, diarrhea occurred in 81% of patients; 20% Grade 3, 1.3% Grade 4
• Left ventricular ejection fraction decrease observed in 9% of patients with chemo plus tislelizumab and 5% with chemo alone; includes a fatal LVD case
• Infusion-related reactions occurred in 22% (chemo plus tislelizumab) and 24% (chemo) despite prophylaxis, including rare Grade 4 events
• Serious adverse reactions occurred in 59% of patients receiving Ziihera with chemotherapy and tislelizumab in HERIZON-GEA-01

News Explained

The FDA approval is based on a Phase 3 trial that remains ongoing, with additional analyses planned; the trial record therefore remains subject to further updates.

Market Reaction – JAZZ

+3.97% $264.38 5.3x vol

15m delay

+3.97% Vs previous close

$264.38 Last Price

$252.02 $266.26 Day Range

$17.18B Market Cap

5.3x Rel. Volume

Following this news, JAZZ has gained 3.97%, reflecting a moderate positive market reaction. Our momentum scanner has triggered 9 alerts so far, indicating moderate trading interest and price volatility. The stock is currently trading at $264.38. Trading volume is exceptionally heavy at 5.3x the average, suggesting very strong buying interest.

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Market Context

Jazz's FDA-approval history showed an average 24-hour move of 0.29%. That platform record frames the...

Analysis

Jazz's FDA-approval history showed an average 24-hour move of 0.29%. That platform record frames the new Ziihera approval, while recent insider activity was net selling and ongoing trial analyses remain a factor to watch.

Key Figures

PFS risk reduction: 35% Median PFS: 12.4 months vs. 8.1 months OS risk reduction: 28% +5 more

8 metrics

PFS risk reduction 35% HERIZON-GEA-01 overall HER2+ population

Median PFS 12.4 months vs. 8.1 months Ziihera-containing combinations vs. trastuzumab plus chemotherapy

OS risk reduction 28% Ziihera plus tislelizumab-jsgr and chemotherapy vs. trastuzumab plus chemotherapy

Median OS 26.4 months vs. 19.2 months Ziihera plus tislelizumab-jsgr and chemotherapy vs. trastuzumab plus chemotherapy

HER2+ disease prevalence Approximately 20% GEA patients

U.S. stomach cancer cases More than 31,000 cases New cases diagnosed annually in the United States

Diarrhea incidence 85% of 330 patients Ziihera with chemotherapy and tislelizumab-jsgr

Fatal diarrhea outcomes 1.5% Ziihera with chemotherapy and tislelizumab-jsgr clinical studies

Previous Fda approval Reports

4 past events · Latest: Oct 02 (Positive)

Same Type Pattern 4 events

Date	Event	Sentiment	24h Move	Catalyst
Oct 02	FDA approval	Positive	+1.6%	Zepzelca and atezolizumab approved for first-line maintenance lung cancer treatment
Aug 06	FDA approval	Positive	-6.4%	Modeyso approved as treatment for recurrent H3 K27M-mutant diffuse midline glioma
Jun 10	FDA priority review	Positive	+1.0%	Zepzelca combination received priority review with an October 7 PDUFA date
Nov 20	FDA approval	Positive	+4.9%	Ziihera approved for previously treated HER2-positive biliary tract cancer

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Jazz's FDA-approval news has produced mostly positive reactions, although one approval event diverged with a 6.42% decline.

Key Terms

bispecific antibody, pd-l1, progression-free survival, overall survival, +2 more

6 terms

bispecific antibody medical

"Ziihera is now the first and only bispecific HER2-targeted antibody"

A bispecific antibody is a specially designed protein that can attach to two different targets at the same time. Think of it as a custom-made connector that brings two things together—such as a disease cell and an immune system component—helping the body fight illnesses more effectively. For investors, understanding bispecific antibodies is important because they represent innovative therapies that could lead to new treatments and potentially lucrative market opportunities.

pd-l1 medical

"regardless of PD-L1 status, establishing a new standard of care"

PD-L1 is a protein found on the surface of some cells that acts like a stop sign for the immune system, telling certain immune cells to back off. It matters to investors because many cancer drugs and diagnostic tests target or measure PD-L1 to unlock immune responses or predict which patients will benefit, affecting clinical success, regulatory approval, and potential sales in the oncology market.

progression-free survival medical

"Progression-free survival (PFS): Both Ziihera-containing combinations"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

overall survival medical

"Overall survival (OS): In the overall HER2+ population"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

lvef medical

"ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF)"

Left ventricular ejection fraction (LVEF) is a percentage that measures how much blood the heart’s main pumping chamber pushes out with each beat, like the share of water a pump empties from a bucket each cycle. Investors watch LVEF because it’s a key medical yardstick used to diagnose and track heart function, shaping demand for drugs, devices, clinical trials, insurance costs and the financial outlook of healthcare-related businesses.

boxed warnings regulatory

"contains Boxed Warnings for diarrhea and embryo-fetal toxicity"

A boxed warning is the strongest safety alert a regulator places on a prescription drug’s label to highlight unusually serious risks, such as life‑threatening side effects or required precautions. Think of it as a prominent danger sticker on a product: it signals higher safety scrutiny and can change how doctors prescribe the drug, affect sales, increase legal and regulatory risk, and therefore influence a company’s revenue and stock value.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Ziihera plus tislelizumab and chemotherapy approved for first-line treatment of all HER2+ GEA patients (IHC 3+ and IHC 2+/ISH+) regardless of PD-L1 status, establishing a new standard of care in front-line GEA

Company to host investor webcast on Aug. 25 at 4:30 p.m. ET

For U.S. media and investors only

DUBLIN, Aug. 25, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the U.S. Food and Drug Administration (FDA) approved two Ziihera^® (zanidatamab-hrii)-containing regimens for the first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive (HER2+) gastroesophageal adenocarcinoma (GEA): Ziihera plus Tevimbra^® (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+), and Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+).

"This approval is a major step forward for people with HER2+ advanced GEA. Ziihera is now the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2+ advanced GEA patients, regardless of PD-L1 status, establishing a new standard of care in first-line treatment," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "The HERIZON-GEA-01 results include the longest median overall survival reported in a Phase 3 trial in this setting, at 26.4 months. We are grateful to the gastric cancer community, including patients, caregivers, investigators and advocacy organizations, whose partnership made this possible."

GEA, which includes gastric, gastroesophageal junction and esophageal cancers, is the fifth most common cancer worldwide and remains associated with poor outcomes despite advances in treatment.¹ Approximately 20% of patients have HER2+ disease.^2,3,4 In the United States, more than 31,000 new stomach cancer cases are diagnosed each year.⁵

"People with advanced HER2+ GEA deserve treatment options that reflect the unique biology of their disease. Understanding what a HER2+ diagnosis means is an important part of navigating treatment decisions and helping patients and families make informed choices about care. Today's approval gives people diagnosed with HER2+ GEA a much-needed new treatment option and more choice in how their cancer is treated," said Martha Raymond, MA, CEO and founder of GI Cancers Alliance.

The approval is based on results from the Phase 3 HERIZON-GEA-01 trial, which were published in the New England Journal of Medicine and first presented at ASCO GI 2026, with PD-L1 subgroup data presented at ASCO 2026. The trial remains ongoing, with additional analyses planned.

Key HERIZON-GEA-01 Results

• Progression-free survival (PFS): Both Ziihera-containing combinations significantly improved PFS in the overall HER2+ population, reducing the risk of disease progression or death by 35% and extending median PFS to 12.4 months versus 8.1 months with trastuzumab plus chemotherapy.
• Overall survival (OS): In the overall HER2+ population, Ziihera plus tislelizumab-jsgr and chemotherapy demonstrated a statistically significant and clinically meaningful OS benefit, reducing the risk of death by 28% compared with trastuzumab plus chemotherapy and achieving a median OS of 26.4 months versus 19.2 months, representing a greater than seven-month improvement and the longest median OS reported in a Phase 3 trial in HER2+ advanced GEA.
• PFS and OS benefits were generally consistent across major prespecified subgroups, including geographic region and PD-L1 status.
• Ziihera-containing regimens demonstrated a manageable safety profile consistent with prior zanidatamab studies, with diarrhea as the most common adverse reaction, predominantly early in onset. Loperamide prophylaxis was administered during the first cycle, and diarrhea was managed with antidiarrheals and treatment modifications as needed, resulting in few discontinuations of Ziihera.

"This approval represents an important advancement in the treatment of metastatic HER2+ GEA," said Geoffrey Ku, M.D., HERIZON-GEA-01 study co-author and associate attending physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. "Importantly, similar outcomes were seen in patients whose tumors were PD-L1 positive or PD-L1 negative, suggesting that this regimen has the potential to benefit a broad range of patients. It further underscores what we have known for more than 15 years: HER2 testing at the time of diagnosis for advanced or metastatic gastroesophageal adenocarcinoma is critical to optimally guide treatment selection."

The company will host an investor webcast on Tuesday, August 25, at 4:30 p.m. ET / 9:30 p.m. IST to discuss the FDA approval of Ziihera in first-line HER2+ GEA and provide updates on the zanidatamab development program. The webcast may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website.

The U.S. Prescribing Information for Ziihera contains Boxed Warnings for diarrhea and embryo-fetal toxicity.

Additional Important Safety Information related to Ziihera use in GEA is provided below. Please see full Prescription, including Boxed Warnings at https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf.

About Gastroesophageal Adenocarcinoma  
GEA, including cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide, and approximately 20% of patients have HER2+ disease.^1,2,3,4 HER2+ GEA has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 10% for metastatic disease.⁶

About Ziihera^® (zanidatamab-hrii)  
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces CDC, ADCC, and ADCP. These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.⁷ 

Gastroesophageal adenocarcinoma (GEA): In the United States, Ziihera is indicated for the first-line treatment of adults with HER2+ locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus, in combination with tislelizumab-jsgr and fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+ as detected by an FDA-authorized test); and in combination with fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ as detected by an FDA-authorized test).

Biliary tract cancer (BTC): In the United States, Ziihera is also indicated for the treatment of adults with previously treated, unresectable or metastatic HER2+ (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.⁷ Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).⁷ Ziihera is also approved in the European Union and other countries.

Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeOne Medicines under license agreements from Zymeworks, which first developed the molecule.  

The FDA granted three Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC, one in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr for first-line HER2+ unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal GEA, and one for the treatment of adults with previously treated, locally advanced, unresectable, or metastatic HER2+ colorectal cancer (CRC). The FDA also granted two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from the FDA for the treatment of BTC, gastric (including GEJ) cancer, and esophageal cancer, as well as Orphan Drug designations from the European Medicines Agency for the treatment of BTC, gastric/gastroesophageal junction cancer, and esophageal cancer. Jazz continues to pursue additional regulatory approvals for zanidatamab in markets worldwide.  

Important Safety Information for ZIIHERA   

WARNING: DIARRHEA and EMBRYO-FETAL TOXICITY ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, can cause severe diarrhea, including life threatening and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated. Interrupt, reduce the dose or discontinue ZIIHERA based on severity.  Embryo-Fetal Toxicity: Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

Diarrhea: ZIIHERA can cause severe diarrhea.

When ZIIHERA is used in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr, severe, life threatening, and fatal cases of diarrhea can occur despite loperamide prophylaxis. The risk of severe and life threatening diarrhea is higher when ZIIHERA is administered with chemotherapy and tislelizumab-jsgr, with a higher risk in patients aged ≥ 65 years compared to younger patients. Advise patients to increase oral fluids, begin antidiarrheals, and notify their healthcare provider immediately if diarrhea occurs.

Administer antidiarrheal prophylaxis with loperamide in cycle 1 for all patients receiving ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr. Begin loperamide at the first loose stool when ZIIHERA is administered in combination with chemotherapy. Administer fluids, electrolytes, and additional antidiarrheal agents as necessary. Before modifying the dose of ZIIHERA, evaluate, modify or discontinue drug(s) contributing to diarrhea in accordance with their respective prescribing information. Withhold, reduce the dose, or permanently discontinue ZIIHERA based on severity.

If treating patients with ZIIHERA in combination with FOLFOX, do not administer the fluorouracil bolus.

ZIIHERA in combination with chemotherapy and tislelizumab-jsgr

Diarrhea was reported in 85% of 330 patients in clinical studies, including Grade 4 (2.1%), Grade 3 (24%), and Grade 2 (31%) events. Fatal outcomes resulting from diarrhea occurred in 1.5% of patients. Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 3.9% of patients.

In cycle 1, diarrhea at Grade 4 severity occurred in 1.5% and Grade 3 severity occurred in 15% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days.

ZIIHERA in combination with chemotherapy

Diarrhea was reported in 81% of 395 patients in clinical studies, including Grade 4 (1.3%), Grade 3 (20%) and Grade 2 (33%). Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 1.8% of patients.

In cycle 1, diarrhea at Grade 4 severity occurred in 0.8% and Grade 3 severity occurred in 14% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days.

Embryo-Fetal Toxicity: Based on the mechanism of action, ZIIHERA can cause fetal harm when administered to a pregnant woman. There are no human or animal data on the use of ZIIHERA in pregnancy. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception while receiving ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction (LVD): ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF).

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is < 50%.

ZIIHERA in combination with chemotherapy and tislelizumab-jsgr

LVEF decrease (an absolute decline in LVEF of > 10%, resulting in a final value of < 50%) was observed in 9% of 330 patients in clinical studies. LVD leading to permanent discontinuation of ZIIHERA was reported in 3% of patients. Fatal outcomes due to LVD occurred in one patient (0.3%). The median time to first occurrence of LVD was 6.9 months (range: 1.2 to 29.1 months). LVD resolved in 78% of patients.

ZIIHERA in combination with chemotherapy

LVEF decrease was observed in 5% of 395 patients. LVD leading to permanent discontinuation of ZIIHERA was reported in 1.0% of patients. The median time to first occurrence of LVD was 6.0 months (range: 1.4 to 15.0 months). LVD dysfunction resolved in 70% of patients.

Infusion-Related Reactions: ZIIHERA can cause infusion-related reactions (IRRs).

Prior to each dose of ZIIHERA, administer premedication to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

ZIIHERA in combination with chemotherapy and tislelizumab-jsgr

An IRR was reported in 22% of 330 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.2%), and Grade 2 (16%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.3% of patients. IRRs occurred on the first day of dosing in 17% of patients. Of all patients who experienced IRRs, 60% of reactions resolved within the first day.

ZIIHERA in combination with chemotherapy

An IRR was reported in 24% of 395 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.5%), and Grade 2 (18%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 1.3% of patients. IRRs occurred on the first day of dosing in 22% of patients. Of all patients who experienced IRRs, 83% of reactions resolved within the first day.

Adverse Reactions

ZIIHERA in combination with chemotherapy and tislelizumab-jsgr

Serious adverse reactions occurred in 59% of 294 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (17%), IRR (5%), vomiting (4.8%), hypokalemia (4.4%), acute kidney injury (3.7%), pneumonia (3.7%), nausea (2.4%), decreased appetite (2.4%), and anemia (2.4%). Fatal adverse reactions occurred in 2.4% of patients and included acute kidney injury (N=2), cardiac failure, diarrhea, dehydration, hypovolemic shock and intestinal obstruction (all N=1).

Permanent discontinuation of ZIIHERA occurred in 13% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included diarrhea (4.4%) and ejection fraction decreased (2.7%).

The most common adverse reactions (≥ 20%) were diarrhea (83%), nausea (56%), decreased appetite (46%), vomiting (44%), hypokalemia (39%), fatigue (37%), rash (36%), peripheral neuropathy (27%), and IRR (25%).

ZIIHERA in combination with chemotherapy

Serious adverse reactions occurred in 49% of 305 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (11%), vomiting (3.3%), decreased appetite (2.6%), pneumonia (2.6%), sepsis (2.6%), hypokalemia (2.3%), and nausea (2.3%).

Permanent discontinuation of ZIIHERA occurred in 10% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included ejection fraction decreased (2.0%), IRR (1.6%), and diarrhea (1.6%).

The most common adverse reactions (≥ 20%) were diarrhea (79%), nausea (54%), vomiting (44%), decreased appetite (40%), fatigue (36%), hypokalemia (33%), peripheral neuropathy (32%), IRR (25%), and rash (22%).

Pediatric Use: Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

ZIIHERA in combination with chemotherapy and tislelizumab-jsgr

Of 302 patients randomized to ZIIHERA in combination with chemotherapy and tislelizumab-jsgr in HERIZON-GEA-01, there were 139 (46%) patients aged ≥65 years. One hundred and six (35%) were aged 65-74 years and 33 (11%) were aged ≥ 75 years.

There was a higher incidence of Grade ≥ 3 adverse reactions observed in patients aged ≥ 65 years (87%) as compared to younger patients (80%). The incidence of Grade 3 or 4 diarrhea was higher in patients aged ≥65 years (32%) compared to younger patients (20%).

There was an increased incidence of fatal adverse reactions in patients aged ≥ 65 years (4.4%); including acute kidney injury (N=2), cardiac failure, dehydration, hypovolemic shock and intestinal obstruction (all N=1), compared to younger patients (0.6%), including diarrhea (N=1). 

ZIIHERA in combination with chemotherapy

Of 304 patients randomized to ZIIHERA in combination with chemotherapy in HERIZON-GEA-01, there were 130 (43%) patients aged ≥ 65 years. One hundred (33%) were aged 65-74 years and 30 (10%) were aged ≥ 75 years.

No overall differences in safety were observed between patients aged ≥ 65 years and younger adult patients.

Dr. Ku has financial interests related to Jazz Pharmaceuticals.

® TEVIMBRA (tislelizumab-jsgr) is a registered trademark of BeOne Medicines.

About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with rare disease — often with limited or no therapeutic options. We have a diverse portfolio of medicines, including leading therapies addressing epilepsies, cancers and sleep disorders. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information. 

Cautionary Note Concerning Forward-Looking Statements 
This press release contains forward-looking statements, including, but not limited to, statements related to the potential therapeutic benefits of zanidatamab and of combination therapies with zanidatamab, zanidatamab's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the successful completion of regulatory activities and uncertain regulatory approval, risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports, including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2025 and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. 

Contacts:

Media: 
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
U.S. +1 215 867 4948

Investor: 
InvestorInfo@jazzpharma.com
Ireland +353 1 634 7800
U.S. +1 650 496 2717

¹ Bray F., et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2024 April; doi.org/10.3322/caac.21834Digital Object Identifier (DOI).
² Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.
³ Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.
⁴ Stroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249.
⁵ American Cancer Society. Key Statistics About Stomach Cancer. American Cancer Society. Updated: February 27, 2026. https://www.cancer.org/cancer/types/stomach-cancer/key-statistics.html.
⁶ Tabernero J., et al. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Taylor & Francis. 2022 July; doi.org/10.2217/fon-2022-0595.
⁷ ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

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SOURCE Jazz Pharmaceuticals plc

FAQ

What did the FDA approve for Jazz Pharmaceuticals (JAZZ) on August 25, 2026?

The FDA approved two Ziihera-based regimens for first-line HER2+ gastroesophageal adenocarcinoma. According to Jazz, Ziihera can now be used with Tevimbra (tislelizumab) plus chemotherapy or with chemotherapy alone in adults with unresectable locally advanced or metastatic HER2-positive GEA.

What were the key overall survival and progression-free survival results for Ziihera in HER2+ GEA?

Ziihera regimens improved both overall survival and progression-free survival versus trastuzumab plus chemotherapy. According to Jazz, median PFS was 12.4 vs 8.1 months and median OS 26.4 vs 19.2 months, with 35% lower risk of progression or death and 28% lower risk of death.

Who is eligible for Ziihera plus tislelizumab and chemotherapy in first-line HER2+ GEA?

Adults with unresectable locally advanced or metastatic HER2-positive GEA are eligible under defined testing criteria. According to Jazz, the Ziihera plus Tevimbra and chemotherapy regimen is indicated for HER2+ IHC 3+ and IHC 2+/ISH+ tumors, as detected by an FDA-authorized test, regardless of PD-L1 status.

What are the main safety warnings and side effects for Ziihera in HER2+ gastroesophageal adenocarcinoma?

Ziihera carries boxed warnings for severe diarrhea and embryo-fetal toxicity. According to Jazz, very high rates of diarrhea, left ventricular dysfunction, and infusion-related reactions were observed, including rare fatal cases, requiring antidiarrheal prophylaxis, cardiac monitoring, contraception counseling, and careful dose modifications based on severity.

Does Ziihera (zanidatamab-hrii) have other approved indications besides HER2+ GEA?

Yes. In the United States, Ziihera is also approved for previously treated unresectable or metastatic HER2-positive biliary tract cancer. According to Jazz, continued approval for this BTC indication may be contingent on confirmatory trials, and Ziihera is approved in the European Union and other countries.

When is Jazz Pharmaceuticals’ webcast about the Ziihera FDA approval, and how can investors access it?

The investor webcast is scheduled for August 25, 2026, at 4:30 p.m. ET. According to Jazz, investors can access the live webcast and later replay through the Investors section of the Jazz Pharmaceuticals website, with registration recommended at least 15 minutes before the start time.

What new standard of care claim is associated with Ziihera in HER2+ GEA?

Jazz states that Ziihera plus tislelizumab and chemotherapy establishes a new first-line standard for HER2+ advanced GEA. According to Jazz, it is the first approved bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy for all HER2+ advanced GEA patients, regardless of PD-L1 status.