Jazz Pharmaceuticals Announces FDA Acceptance and Priority Review of Supplemental Biologics License Application for Ziihera® (zanidatamab-hrii) Combinations in First-Line HER2+ Locally Advanced or Metastatic GEA

Rhea-AI Summary

Jazz Pharmaceuticals (Nasdaq: JAZZ) announced FDA acceptance with Priority Review of an sBLA for Ziihera (zanidatamab-hrii) combinations as first-line therapy for adult patients with HER2+ unresectable locally advanced or metastatic gastric, GEJ, or gastroesophageal adenocarcinoma (GEA).

The FDA set a PDUFA target action date of August 25, 2026. The submission uses the RTOR program and is supported by pivotal HERIZON-GEA-01 data showing added benefit when combining zanidatamab with chemotherapy ± tislelizumab. The FDA previously granted Breakthrough Therapy designation for these combinations.

Positive

• PDUFA target action date set for August 25, 2026
• sBLA accepted with Priority Review by FDA
• Submission reviewed via FDA Real-Time Oncology Review (RTOR)
• FDA granted Breakthrough Therapy designation for the combinations
• HERIZON-GEA-01 showed added clinical benefit with tislelizumab

Negative

• Regulatory approval is pending; decision not guaranteed by Aug 25, 2026
• Labeling, postmarketing requirements, or additional data may be required by FDA

News Market Reaction – JAZZ

+2.39%

1 alert

+2.39% Session close to close

$12.80B Market Cap

0.0x Rel. Volume

In the Apr 27 session, JAZZ gained 2.39%, reflecting a moderate positive market reaction.

Data tracked by StockTitan Argus on the day of publication.

Market Context

This announcement details FDA acceptance and Priority Review of an sBLA for Ziihera combinations in ...

Analysis

This announcement details FDA acceptance and Priority Review of an sBLA for Ziihera combinations in first-line HER2+ locally advanced or metastatic GEA, with a PDUFA target date of August 25, 2026. The filing is supported by the pivotal HERIZON-GEA-01 trial and is being reviewed under the RTOR program, alongside Breakthrough Therapy designation. In context of Jazz’s recent stream of clinical and medical-education updates, investors may watch for further regulatory milestones and detailed efficacy and safety data from the trial.

Key Figures

PDUFA date: August 25, 2026 Xywav revenue: $1,657.0 million Epidiolex/Epidyolex revenue: $1,059.2 million +5 more

8 metrics

PDUFA date August 25, 2026 FDA target action date for Ziihera sBLA in HER2+ GEA

Xywav revenue $1,657.0 million 2025 product sales reported in 10-K/A

Epidiolex/Epidyolex revenue $1,059.2 million 2025 product sales reported in 10-K/A

Non-affiliate equity value $6.25 billion Aggregate market value as of June 30, 2025

Shares outstanding 62,738,815 shares Ordinary shares outstanding as of April 15, 2026

2025 bonuses 150% of target Corporate bonus funding based on 2025 goals

2023–2025 PSUs payout 94% of target Performance share units after scoring and TSR adjustment

Proposed share sale 6,000 shares Form 144 proposed sale notice dated 04/01/2026

Historical Context

5 past events · Latest: Apr 21 (Neutral)

Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Apr 21	Earnings timing update	Neutral	+0.8%	Announcement of Q1 2026 earnings release date and post-close webcast.
Apr 21	Clinical data plans	Neutral	+0.8%	Planned ASCO 2026 presentations for Ziihera and Zepzelca clinical data.
Apr 09	Neurology data	Neutral	+1.1%	AAN 2026 abstracts on Epidiolex and Xywav, including seizure and narcolepsy data.
Apr 01	Investor conference	Neutral	-0.7%	Participation in Needham Healthcare Conference with scheduled fireside chat.
Mar 24	Education initiative	Neutral	+1.5%	Collaboration on sodium reduction and cardiovascular health education in sleep disorders.

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

Pattern Detected

Recent Jazz headlines, including conference participation and data presentations, generally saw modestly positive or limited price reactions, suggesting balanced sentiment to routine news.

Recent Company History

Over the last month, Jazz has highlighted upcoming financial results, multiple conference presentations, and a cardiovascular education initiative. News on March 24, 2026 about a sodium-reduction initiative, and April medical meeting updates tied to Epidiolex, Xywav, and Ziihera were followed by modest gains of up to 1.48%. An investor conference announcement on April 1, 2026 coincided with a small decline of 0.7%. Today’s FDA priority review update fits into a pattern of frequent pipeline and medical-education communications.

Key Terms

prescription drug user fee act (pdufa), pdufa, supplemental biologics license application (sbla), real-time oncology review (rtor), +3 more

7 terms

prescription drug user fee act (pdufa) regulatory

"Prescription Drug User Fee Act (PDUFA) date set for August 25, 2026"

The Prescription Drug User Fee Act (PDUFA) is a law that allows drug companies to pay fees to the government to help speed up the review process for new medicines. This funding aims to ensure that important drugs reach patients faster, which can influence a company's ability to bring products to market efficiently. For investors, PDUFA-related decisions can impact drug approval timelines and company performance.

pdufa regulatory

"The FDA has set a PDUFA target action date of August 25, 2026."

PDUFA is the Prescription Drug User Fee Act, the U.S. law under which drug companies pay fees that fund the FDA's review of new medicines. In company news the term usually appears as the PDUFA date, the target deadline by which the FDA aims to decide on a drug application; that date tells investors when to expect the approval or rejection decision for the product.

supplemental biologics license application (sbla) regulatory

"accepted for filing with Priority Review the supplemental Biologics License Application (sBLA)"

A supplemental biologics license application (sBLA) is a formal request to a drug regulator to approve a change to a biologic product that already has a license, such as a new use, manufacturing process, dosage form, or labeling update. Investors care because approval can expand sales or reduce costs, while rejection or delay can create regulatory risk and affect revenue; think of it as asking permission to alter a proven recipe before selling the new version.

real-time oncology review (rtor) regulatory

"under review via the Real-Time Oncology Review (RTOR) program"

Real-Time Oncology Review (RTOR) is a regulatory program that lets drug regulators review key clinical data as it becomes available instead of waiting for a finished application, so the assessment can proceed in parallel with the company's final submission. For investors, RTOR matters because it can shorten the time between final data and a decision—like letting an inspector check a building while it's being finished—reducing approval uncertainty and potentially accelerating a therapy’s market entry and revenue timing.

rtor regulatory

"under review via the Real-Time Oncology Review (RTOR) program"

RTOR stands for Real-Time Oncology Review, a regulatory program run by the U.S. Food and Drug Administration that lets drug developers share clinical data with reviewers as it becomes available instead of waiting until the full application is finished. For investors, RTOR can shorten the time between final trial results and a regulatory decision—like letting a reviewer read key chapters of a book early—reducing timing uncertainty and potentially accelerating a drug’s market access and revenue timeline.

breakthrough therapy designation regulatory

"The FDA granted Breakthrough Therapy designation to zanidatamab in combination with"

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

pd-1 inhibitor medical

"with or without the PD-1 inhibitor Tevimbra® (tislelizumab) in patients"

A PD-1 inhibitor is a type of medicine that helps the immune system recognize and attack cancer cells by blocking the PD-1 checkpoint—a molecular “off switch” that cancer can use to hide from immune defenses. For investors, these drugs matter because they can transform treatment options, drive sales or partnerships, and affect a company’s valuation if clinical trials, approvals, or competitive positioning change; think of them as unlocking a locked door to let the body’s defenses work.

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

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Prescription Drug User Fee Act (PDUFA) date set for August 25, 2026

For U.S. media and investors only

DUBLIN, April 27, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the U.S. Food and Drug Administration (FDA) accepted for filing with Priority Review the supplemental Biologics License Application (sBLA) for Ziihera^® (zanidatamab-hrii) containing combinations for the first-line treatment of adult patients with HER2-positive (HER2+) unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or gastroesophageal adenocarcinoma (GEA). The FDA has set a PDUFA target action date of August 25, 2026.

The sBLA is supported by data from the pivotal HERIZON-GEA-01 trial to investigate the efficacy and safety of zanidatamab in combination with standard-of-care chemotherapy with or without the PD-1 inhibitor Tevimbra^® (tislelizumab) in patients with advanced or metastatic GEA, including gastric, GEJ and esophageal adenocarcinomas. The submission is under review via the Real-Time Oncology Review (RTOR) program, an initiative of FDA's Oncology Center of Excellence designed to provide a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

"The HERIZON-GEA-01 trial results are practice changing, supporting the potential of zanidatamab as the HER2-targeted agent-of-choice in HER2+ first-line locally advanced or metastatic GEA. Importantly, the results demonstrated adding tislelizumab to zanidatamab plus chemotherapy further enhanced clinical benefit and marked the first immuno-oncology combination to show efficacy across both PD-L1–positive and PD-L1–negative tumors in this clinical setting," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of R&D, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to work closely with FDA to obtain approval and quickly bring zanidatamab to market for GEA patients in need of new options."

The FDA granted Breakthrough Therapy designation to zanidatamab in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab, for the first-line treatment of patients with HER2+ unresectable locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Breakthrough Therapy designation is intended to expedite the development and review of therapies that, based on preliminary clinical evidence, may offer substantial improvement over available therapies on one or more clinically significant endpoints, reflecting both the seriousness of the disease and the unmet medical need in this setting.

About the Phase 3 HERIZON-GEA-01 Trial
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with BeOne Medicines, to evaluate and compare the efficacy and safety of zanidatamab plus chemotherapy, with or without tislelizumab, to trastuzumab plus chemotherapy as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Appropriate patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: zanidatamab in combination with chemotherapy and tislelizumab; zanidatamab in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS. Results from the trial were presented in January 2026 at the 2026 ASCO Gastrointestinal Cancers Symposium.

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 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 30% for gastric cancer and about 19% for GEA.⁴

About Ziihera^® (zanidatamab-hrii)  
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.⁵ In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.¹ The FDA granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).¹ 

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 Pharmaceuticals and BeOne under license agreements from Zymeworks, which first developed the molecule.   

An sBLA for zanidatamab is being reviewed by the FDA under RTOR in first-line HER2+ locally advanced or metastatic GEA. The FDA granted two Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC, and one in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab for first-line HER2+ unresectable locally advanced or metastatic gastric, GEJ or esophageal adenocarcinoma. 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/GEJ cancer and oesophageal cancer. 

 Important Safety Information for ZIIHERA   

WARNING: EMBRYO-FETAL TOXICITY  Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients  of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS 

Embryo-Fetal Toxicity
ZIIHERA can cause fetal harm when administered to a pregnant woman. 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 during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA. 

Left Ventricular Dysfunction
ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients. 

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 below 50%. 

Infusion-Related Reactions
ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day. 

Prior to each dose of ZIIHERA, administer premedications 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. 

Diarrhea
ZIIHERA can cause severe diarrhea. 

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity. 

ADVERSE REACTIONS
Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA. 

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%). 

USE IN SPECIFIC POPULATIONS 

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

Geriatric Use
Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older. 

No overall differences in safety or efficacy were observed between these patients and younger adult patients. 

The full U.S. Prescribing Information for ZIIHERA, including BOXED Warning, is available at: https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf 

® TEVIMBRA (tislelizumab) 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 potentially life-changing medicines for people with rare disease — often with limited or no therapeutic options. We have a diverse portfolio of marketed 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 Ziihera (zanidatamab-hrii) 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, expected timing of and ability to obtain FDA approval under the RTOR program for zanidatamab in HER2+ first-line GEA 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 3211
U.S. +1 650 496 2717

¹Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.
²Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.
³Stroes, 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.
⁴Battaglin F, et al. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell International. 2018;18(99).
⁵ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.

 

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SOURCE Jazz Pharmaceuticals plc

FAQ

What is the FDA PDUFA date for Jazz Pharmaceuticals' Ziihera (JAZZ) sBLA for first-line HER2+ GEA?

The FDA set a PDUFA target action date of August 25, 2026. According to Jazz Pharmaceuticals, this is the target date for the agency's decision on the Priority Review submission.

What does Priority Review and RTOR mean for the JAZZ Ziihera sBLA timeline?

Priority Review shortens the FDA review goal; RTOR enables rolling, expedited assessment. According to Jazz Pharmaceuticals, the sBLA is being reviewed under both programs to accelerate evaluation.

What clinical evidence supports Jazz's Ziihera sBLA for HER2+ first-line GEA?

The sBLA is supported by data from the pivotal HERIZON-GEA-01 trial. According to Jazz Pharmaceuticals, the trial showed added benefit when zanidatamab was combined with chemotherapy with or without tislelizumab.

Did the FDA grant any special designations for zanidatamab combinations (JAZZ)?

Yes. The FDA granted Breakthrough Therapy designation for zanidatamab with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab. According to Jazz Pharmaceuticals, this reflects preliminary evidence of substantial improvement over available therapies.

How does adding tislelizumab affect the zanidatamab combination in HERIZON-GEA-01?

Adding tislelizumab reportedly enhanced clinical benefit versus zanidatamab plus chemotherapy alone. According to Jazz Pharmaceuticals, the combination showed efficacy across both PD-L1–positive and PD-L1–negative tumors in the trial.