On December 3, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported that it has amended the 2021 clinical supply agreement with Regeneron for the expansion portion of THIO-101, its Phase 2 clinical trial evaluating THIO in sequential administration with cemiplimab (Libtayo) (Press release, MAIA Biotechnology, DEC 3, 2024, View Source [SID1234648777]). The new expansion will further assess the efficacy of MAIA’s lead asset, THIO, sequenced with immune checkpoint inhibitor (CPI) Libtayo (cemiplimab) for advanced non-small cell lung cancer (NSCLC) patients receiving third-line therapy who were resistant to previous checkpoint inhibitor treatments and chemotherapy.

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The original 2021 agreement between MAIA and Regeneron was designed to supply the original THIO-101 trial through the dose selection and safety evaluation process. The THIO-101 trial has been amended and expanded to further evaluate efficacy at the target dose and target third line patient population.

"In keeping with our clinical strategy for THIO, we look forward to continuing our collaboration with Regeneron to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. So far, THIO-101 has demonstrated favorable disease control, progression free survival, overall response rates, and we remain on track to achieve our overall survival goals," said MAIA Chairman and Chief Executive Officer Vlad Vitoc, M.D.

Under terms of the amended clinical supply agreement, MAIA continues to sponsor THIO-101 and Regeneron will provide Libtayo for the treatment of all patients in the trial including the additional patients in the THIO 101 expansion. MAIA holds an exclusive worldwide patent license to develop and commercialize THIO.

MAIA expects to start enrolling new patients in the expansion of THIO-101 in the near future.

The company continues to evaluate its regulatory strategy and believes that there could be an opportunity for an accelerated approval in the United States based on the ultimate outcome of the ongoing THIO 101 trial.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with THIO followed by cemiplimab (Libtayo) has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On December 3, 2024 Kairos Pharma Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company developing therapies to surmount current cancer drug resistance and immune suppression, reported the addition of City of Hope Cancer Center in Duarte, California to the Phase 2 clinical trial for ENV105 for castrate-resistant prostate cancer patients (Press release, Kairos Pharma, DEC 3, 2024, View Source [SID1234648776]).

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City of Hope Cancer Center is the first of several planned new centers to be added in the coming weeks to support the Company’s randomized trial for patients receiving either apalutamide or apalutamide+ENV105 combination therapy. The additional centers allow Kairos Pharma to test ENV105 in a broader patient population to identify blood markers that could help select patients expected to benefit most from ENV105 treatment. The trial is supported by Kairos Pharma Ltd. and a grant from the National Cancer Institute (NCI).

Kairos Pharma Chief Scientific Officer Dr. Neil Bhowmick said, "The preclinical findings suggest that ENV105 blocks a central mechanism of hormone therapy resistance. We are encouraged that we have multiple peer-reviewed articles in addition to receiving an NCI grant that supports the solid science behind this trial. We are fortunate to be working with the talented and experienced oncologists at City of Hope, who will be key participants in a trial that may provide patients with a new alternative to the current standard of care."

Kairos CEO Dr. John Yu added, "This is an important milestone in our mission to develop first-in-class approaches to address the inevitable resistance that develops in prostate cancer patients receiving hormone therapy, as it provides additional validation for the science behind ENV105. City of Hope is a first-class research institution, and we look forward to our continued collaboration with them."

On December 3, 2024 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported that it has commenced an underwritten public offering of $300.0 million of shares of its common stock or, in lieu of common stock issued to certain investors that so choose, pre-funded warrants to purchase shares of its common stock (Press release, Janux Therapeutics, DEC 3, 2024, View Source [SID1234648775]). In addition, Janux expects to grant the underwriters a 30-day option to purchase up to an additional $45.0 million of shares of its common stock at the public offering price, less the underwriting discounts and commissions. All of the securities to be sold in the offering are to be sold by Janux. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

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BofA Securities, TD Cowen, Stifel, Cantor and William Blair are acting as joint book-running managers for the offering. Wedbush PacGrow, LifeSci Capital, BTIG and Jones are acting as co-managers for the offering.

The Company intends to use the net proceeds from the offering to advance clinical development of its internal product pipeline and for general corporate purposes.

The securities are being offered by the company pursuant to a Registration Statement on Form S-3 filed with the Securities and Exchange Commission (SEC) that became automatically effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from: BofA Securities, NC1-022-02-25, 201 North Tryon Street, Charlotte, North Carolina 28255-0001, Attention: Prospectus Department, or by email at [email protected]; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by telephone at (855) 495-9846 or by email at [email protected]; Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, California 94104, by telephone at (415) 364-2720, or by email at [email protected]; Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by email at [email protected]; or William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, Illinois 60606, by telephone at (800) 621-0687 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 3, 2024 K36 Therapeutics, Inc. ("K36"), a clinical-stage biotech company focused on developing its first-in-class MMSET / NSD2 inhibitor KTX-1001 for t(4;14) multiple myeloma, reported upcoming poster presentations outlining data from its KTX-1001 and KTX-1029 programs at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition held December 6-10, 2024 in San Diego, California (Press release, K36 Therapeutics, DEC 3, 2024, View Source [SID1234648774]).

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The KTX-1001 presentations will feature the first results from the dose escalation part of the Phase 1 study and characterization of the asset’s biochemical activity. A third poster will characterize the in vitro and in vivo efficacy of KTX-1029, a novel, potent, selective inhibitor of MMSET. Taken together, the results collectively support the mechanism of action and rationale for targeting MMSET in patients with multiple myeloma.

"I am excited to report on the clinical progress of KTX-1001, a potent, oral MMSET inhibitor being developed for multiple myeloma patients with translocation t(4;14). The dose-escalation phase of the clinical trial demonstrates an increase in KTX-1001 exposure by dose and a corresponding decrease in H3K36me2 biomarker, reflecting clear target engagement that is consistent with preclinical models" said Pierre Bories, MD, PhD, Hematologist, Early Phase Clinical Research Unit Hematology and Clinical Research, Onco-Occitanie Network, Toulouse University Cancer Institute Oncopole.

"We’ve seen significant momentum in enrollment since our first presentation at ASH (Free ASH Whitepaper) last year, highlighting the opportunity for KTX-1001 to meet the unmet need for oral therapies in high-risk patients," said Terry Connolly, Ph.D., President and Chief Executive Officer of K36. "I want to thank the patients, investigators, and their teams for their commitment to generating crucial data from our trial. KTX-1001 has shown a favorable tolerability profile, and promising clinical activity reinforcing its potential as a first in class targeted therapy for t(4;14) multiple myeloma patients who have exhausted standard treatments."

Additional presentation details are outlined below:

Title: First Results from the Dose Escalation Part of the Phase 1 Study of KTX1001, an Oral, First-in-Class, Potent Inhibitor of MMSET/NSD2 for Relapsed/Refractory Multiple Myeloma (RRMM)
Poster Number: 3370
Session Name: 654. Multiple Myeloma: Pharmacologic Therapies: Poster II
Date & Time: Sunday, December 8, 2024, 6:00 PM-8:00 PM PST

"This trial highlights the potential of personalized oral therapies like KTX-1001 to treat multiple myeloma with a targeted medicine designed for high-risk patients," said Benjamin Winograd, M.D. Ph.D., K36’s Chief Medical Officer. "The safety profile of the oral therapy at relevant doses allows us to move forward with the dose expansion phase of the trial. In 2025, we will combine our oral investigational drug with standard of care agents, starting with a proteasome inhibitor and IMiDS to continue the development of KTX-1001 for the treatment of t(4;14) patients"

Title: Characterization of the Biochemical Activity of KTX-1001, a Selective Small Molecule NSD2 Inhibitor, in Surface Plasmon Resonance (SPR)
Poster Number: 2205
Session Name: 802. Chemical Biology and Experimental Therapeutics
Date & Time: Saturday, December 7, 2024, 5:30 PM-7:30 PM PST

Describes a novel method for utilizing surface plasmon resonance (SPR) to interrogate the binding of KTX-1001 to the SET domain of MMSET.
These data demonstrate that one of the ways that KTX-1001 reduces H3K36me2 is by displacing S-adenosyl methionine (SAM), the cofactor responsible for donating the methyl groups to H3K36.
Title: KTX-1029, a Potent, Selective MMSET/NSD2 Inhibitor Is Effective in t(4;14) Multiple Myeloma Preclinical Models
Poster Number: 1878
Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias
Date & Time: Saturday, December 7, 2024, 5:30 PM-7:30 PM PST

Describes the in vitro and in vivo efficacy of KTX-1029, a novel, potent, selective inhibitor of MMSET. KTX-1029 demonstrated efficacy in MM preclinical models as a single agent and in combination with the proteasome inhibitors bortezomib and carfilzomib in both PI-sensitive and -resistant settings.
The data generated with KTX-1029 compliments the data generated with the company’s orally-available clinical candidate, KTX-1001 and adds to the body of evidence for targeting MMSET in multiple myeloma patients with t(4;14) and for further exploration of combination regimens with multiple myeloma standards of care.
Full abstracts can be found at the ASH (Free ASH Whitepaper) Annual Meeting website at www.Hematology.org.

About KTX-1001
KTX-1001 is a novel, first-in-class, potent, and selective methyltransferase inhibitor of the catalytic activity of MMSET/NSD2. It is an orally administered small molecule developed initially for the treatment of relapsed and refractory multiple myeloma, with a focus on patients with the t(4;14) translocation. This inhibitor offers a promising avenue for addressing this challenging high risk patient population.

About the KTX-1001 Phase 1 Clinical Trial
The Phase 1 clinical trial is a single-arm, open-label study in subjects with relapsed and refractory multiple myeloma. It is a multi-part clinical trial with dose escalation followed by an expansion cohort in patients with the genetic translocation t(4;14) to evaluate the safety, tolerability, and preliminary efficacy of different doses of KTX-1001. For more information and participating centers visit NCT05651932.

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

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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.