On December 3, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Company and its partners will present two abstracts at the 2024 San Antonio Breast Cancer Symposium (SABCS) from December 10-13 and 13 abstracts at the 66th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 7-10 (Press release, Jazz Pharmaceuticals, DEC 3, 2024, View Source [SID1234648772]).
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A trial-in-progress poster presentation at SABCS outlines the trial design of the ongoing Phase 3 EmpowHER-303 trial (NCT06435429), which is evaluating the efficacy and safety of Ziihera (zanidatamab-hrii) vs trastuzumab with chemotherapy in patients with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, trastuzumab deruxtecan. New data from a Phase 1b/2 study of zanidatamab plus evorpacept (NCT05027139) in patients with pre-treated HER2-positive and HER2-low metastatic breast cancer will be featured as a poster spotlight.
"Following the recent FDA approval of Ziihera for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, we are pleased to present meaningful data at SABCS on the positive impact zanidatamab can have for patients with HER2-expressing cancers. We continue to advance our clinical program for zanidatamab with the goal to improve outcomes for patients with difficult-to-treat HER2-positive cancers. Our development program includes multiple ongoing Phase 3 trials evaluating 1L BTC, 1L GEA, with top-line PFS results expected in the second quarter of 2025, and metastatic breast cancer after T-DXd treatment, supporting the use of zanidatamab after other HER2-targeted therapies," 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. "Additionally, we look forward to highlighting 13 abstracts featuring oncology research at ASH (Free ASH Whitepaper) 2024, which underscores our commitment to improving standards of care in blood cancer and other hematologic diseases."
The full SABCS abstracts are available here. The Jazz and partner-supported presentations at SABCS 2024 are:
Ziihera (zanidatamab-hrii) Presentations
Topic
Author
Presentation Details
EmpowHER 303: A phase 3 study to
evaluate the efficacy and safety of
zanidatamab vs trastuzumab with
chemotherapy in patients (pts) with
metastatic HER2-positive breast
cancer who have progressed on, or are
intolerant to, trastuzumab deruxtecan
Sara M Tolaney, et al.
Presentation Type: Poster Session
Abstract Number: SESS-1922
Date: Friday December 13, 2024
Time: 12:00-2:00 PM (PST)
Zanidatamab in combination with
evorpacept in HER2-positive and
HER2-low metastatic breast cancer:
Results from a phase 1b/2 study
Alberto J Montero, et al.
Presentation Type: Poster Spotlight Presentation
Abstract Number: SESS-2007
Date: Thursday December 12, 2024
Time: 7:00-8:30 AM (PST)
The full ASH (Free ASH Whitepaper) abstracts are available here. The Jazz and partner-supported presentations at ASH (Free ASH Whitepaper) 2024 are:
Vyxeos (daunorubicin and cytarabine) Presentations
Topic
Author
Presentation Details
A Randomized Comparison of CPX-
351 and FLAG-Ida in Patients With
High-Risk Acute Myeloid Leukemia
(AML)/Myelodysplastic Syndrome
(MDS) And MDS-Related Gene
Mutations: A Subgroup Analysis of the
UK NCRI AML19 Trial
Priyanka Mehta, et al.
Presentation Type: Oral Presentation
Abstract Number: #55
Date: Saturday December 7, 2024
Time: 9:30 AM (PST)
AML-MR Mutations Drive the Benefit of
CPX-351 over 7+3 in the Pivotal Phase
3 AML Trial
Shai O Shimony, et al.
Presentation Type: Oral Presentation
Abstract Number: #60
Date: Saturday December 7, 2024
Time: 10:45 AM (PST)
Phase Ib/II Study of CPX-351 in
Combination with Venetoclax in
Patients with Newly Diagnosed, High
Risk Acute Myeloid Leukemia
Emmanuel Almanza, et al.
Presentation Type: Poster Presentation
Abstract Number: #1511
Date: Saturday December 7, 2024
Time: 5:30-7:30 PM (PST)
A Randomised Comparison of CPX-
351 versus Standard Daunorubicin and
Cytarabine plus Fractionated
Gemtuzumab Ozogamicin in Older
AML Adults Without Known Adverse
Risk Cytogenetics: Results of the NCRI
AML18 Trial
Steven Knapper, et al.
Presentation Type: Oral Presentation
Abstract Number: #59
Date: Saturday December 7, 2024
Time: 10:30 AM (PST)
Phase 1/1b Dose Escalation and
Expansion of CPX-351 in Combination
with Gemtuzumab Ozogamicin in
Newly Diagnosed Acute Myeloid
Leukemia
Onyee Chan, et al.
Presentation Type: Poster Presentation
Abstract Number: #4270
Date: Monday December 9, 2024
Time: 6:00-8:00 PM (PST)
A Phase 3 Randomized Trial for
Patients with de novo AML Comparing
Standard Therapy Including
Gemtuzumab Ozogamicin (GO) to
CPX-351 with GO – A report from the
Children’s Oncology Group
Jessica A Pollard, et al.
Presentation Type: Oral Presentation
Abstract Number: #967
Date: Monday December 9, 2024
Time: 4:30 PM (PST)
Combination of CPX-351 and
Gemtuzumab Ozogamicin (GO) in
Relapsed Refractory (R/R) Acute
Myeloid Leukemia and Post
Hypomethylating Agent (HMA) Failure
High-Risk Myelodysplastic Syndrome
(HR-MDS)
Jayastu Senapati, et al.
Presentation Type: Poster Presentation
Abstract Number: #2903
Date: Sunday December 8, 2024
Time: 6:00-8:00 PM (PST)
Phase Ib/II Study of CPX-351 plus
Venetoclax in Patients with
Relapsed/Refractory Acute Myeloid
Leukemia (AML)
Vanthana Bharathi, et al.
Presentation Type: Poster Presentation
Abstract Number: #4272
Date: Monday December 9, 2024
Time: 6:00-8:00 PM (PST)
Rapid, Reliable, and Comprehensive
Identification of MDS-Defining
Cytogenetic Changes By a FISH-Panel
Containing Six Probes in a Real-World
Population of Patients with Suspected
AML
Katayoon Shirneshan, et al.
Presentation Type: Poster Presentation
Abstract Number: #4308
Date: Monday December 9, 2024
Time: 6:00-8:00 PM (PST)
Prospective Evaluation of the Impact of
Measurable Residual Disease (MRD)
by Error Corrected Next-Generation
Sequencing (NGS) with CPX-351 in
Acute Myeloid Leukemia (AML)
David Sallman, et al.
Presentation Type: Poster Presentation
Abstract Number: #4332
Date: Monday December 9, 2024
Time: 6:00-8:00 PM (PST)
A Phase 1 Study of CPX-351 Plus
Gilteritinib in Relapsed or Refractory,
FLT3-Mutated Acute Myeloid Leukemia
Onyee Chan, et al.
Presentation Type: Poster Presentation
Abstract Number: #1520
Date: Saturday December 7, 2024
Time: 5:30-7:30 PM (PST)
Defitelio (defibrotide sodium) Presentations
Topic
Author
Presentation Details
Genetic Susceptibility in Sinusoidal
Obstruction Syndrome/Veno-Occlusive
Disease
Ioulia Mavrikou, et al.
Presentation Type: Poster presentation
Abstract Number: #4778
Date: Monday December 9, 2024
Time: 6:00-8:00 PM (PST)
Defibrotide reduces hypercoagulable
state in patients with Sickle Cell
Disease-Related Acute Chest
Syndrome
Edo Schaefer, et al.
Presentation Type: Poster presentation
Abstract Number: #2515
Date: Sunday December 8, 2024
Time: 6:00-8:00 PM (PST)
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 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.1 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 U.S. Food and Drug Administration (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 not approved anywhere else in the world.
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 BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric 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.
About Vyxeos (daunorubicin and cytarabine) liposome for injection
Vyxeos is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor.
In the U.S., Vyxeos (daunorubicin and cytarabine) liposome for injection is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.3
More information about Vyxeos in the United States, including Full Prescribing Information and BOXED Warning, is available here.
Important Safety Information for VYXEOS
WARNING: VYXEOS has different dosage recommendations from other medications that contain daunorubicin and/or cytarabine. Do not substitute VYXEOS for other daunorubicin and/or cytarabine-containing products.
VYXEOS should not be given to patients who have a history of serious allergic reaction to daunorubicin, cytarabine, or any of its ingredients.
VYXEOS can cause a severe decrease in blood cells (red and white blood cells and cells that prevent bleeding, called platelets) which can result in serious infection or bleeding and possibly lead to death. Your doctor will monitor your blood counts during treatment with VYXEOS. Patients should tell the doctor about new onset fever or symptoms of infection or if they notice signs of bruising or bleeding.
VYXEOS can cause heart-related side effects. Tell your doctor about any history of heart disease, radiation to the chest, or previous chemotherapy. Inform your doctor if you develop symptoms of heart failure such as:
shortness of breath or trouble breathing
swelling or fluid retention, especially in the feet, ankles, or legs
unusual tiredness
VYXEOS may cause allergic reactions including anaphylaxis. Seek immediate medical attention if you develop signs and symptoms of anaphylaxis such as:
trouble breathing
severe itching
skin rash or hives
swelling of the face, lips, mouth, or tongue
VYXEOS contains copper and may cause copper overload in patients with Wilson’s disease or other copper-processing disorders.
VYXEOS can damage the skin if it leaks out of the vein. Tell your doctor right away if you experience symptoms of burning, stinging, or blisters and skin sores at the injection site.
VYXEOS can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Do not breastfeed while receiving VYXEOS. Females and males of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of VYXEOS.
The most common side effects are bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.
Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568.
About Defitelio (defibrotide sodium)
In the U.S., Defitelio (defibrotide sodium) injection 80mg/mL received U.S. Food and Drug Administration (FDA) marketing approval on March 30, 2016, and it is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication.6
Please see full Prescribing Information for Defitelio in the United States.
In Europe, defibrotide is marketed under the name Defitelio ▼ (defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients after HSCT therapy. In Europe, Defitelio is indicated in patients over one month of age.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC
The full Summary of Product Characteristics of Defitelio in Europe is available here.
Important Safety Information for Defitelio
Defitelio should not be given to patients who are:
Currently taking anticoagulants or fibrinolytics
Allergic to Defitelio or any of its ingredients
Defitelio may increase the risk of bleeding in patients with VOD and should not be given to patients with active bleeding. During treatment with Defitelio, patients should be monitored for signs of bleeding. In the event that bleeding occurs during treatment with Defitelio, treatment should be temporarily or permanently stopped.
Patients should tell the doctor right away about any signs or symptoms of hemorrhage such as unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, or altered vision.
Defitelio may cause allergic reactions including anaphylaxis. Patients who develop signs and symptoms of anaphylaxis such as trouble breathing, severe itching, skin rash or hives, or swelling of the face, lips, mouth or tongue should seek medical attention immediately.
The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.
Defitelio is not approved for the prevention of VOD. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy.