Jazz Pharmaceuticals to Present New Data at the Annual ASH Meeting

Eleven Presentations Evaluating Marketed and Investigational Compounds for Hepatic Veno-Occlusive Disease (VOD) and Acute Myeloid Leukemia (AML)

Presentations Include a Sub-Analysis of Phase 3 Data for Vyxeos (CPX-351), an investigational product for the treatment of AML Patients

DUBLIN, Nov. 7, 2016 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) announced today that eleven abstracts, including four oral presentations, supporting the company's hematology and oncology portfolio will be presented at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California, December 3-6, 2016.

"The data presentations at ASH reflect our efforts in advancing our diversified pipeline of programs in hematology and oncology, including rare blood disorders such as acute lymphoblastic leukemia (ALL) and AML, and in complications of hematopoietic stem-cell transplantation (HSCT) such as hepatic VOD," said Karen Smith, M.D., Ph.D., global head of research and development and chief medical officer at Jazz Pharmaceuticals.  "Of note, we look forward to sharing a post-hoc sub-analysis of Phase 3 survival data following allogeneic HSCT in older high-risk AML patients that compares CPX-351, also known as Vyxeos, with the standard of care."

The following oral and poster presentations focusing on Defitelio® (defibrotide sodium) injection, Erwinaze® (asparaginase Erwinia chrysanthemi) and CPX-351(cytarabine and daunorubicin liposome injection) will be presented at ASH.

Defitelio Related Oral and Poster Presentations

VOD Related Abstract

Erwinaze Related Oral and Poster Presentations

CPX-351 Related Oral and Poster Presentations

AML Related Poster

Additionally, one Jazz-sponsored Investigator Initiated Research poster presentation focusing on CPX-351 as an investigational agent for the treatment of AML will be presented at ASH.

Full details of the ASH 2016 annual meeting can be found here (http://www.hematology.org/Annual-Meeting/) and abstracts can be found here (https://ash.confex.com/ash/2016/webprogram/start.html).

About Defitelio¹ 
In the U.S., Defitelio® (defibrotide sodium) injection 80mg/mL received FDA marketing approval on March 30, 2016 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.

Defitelio is contraindicated in patients currently taking anticoagulants or fibrinolytics and in patients who are allergic to Defitelio or any of its ingredients.  Defitelio may increase the risk of bleeding and should be withheld or stopped if significant bleeding occurs.  Patients should be monitored for allergic reactions, especially if there is a history of previous exposure to Defitelio.  The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.

Please see full Prescribing Information for Defitelio. (https://defitelio.com/DefitelioPI.pdf)

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 undergoing HSCT therapy.  It is the first and only approved treatment in Europe for severe VOD.  In Europe, Defitelio is indicated in patients over one month of age.  It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy. ▼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. (http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/human/medicines/002393/human_med_001646.jsp)

About VOD    
HSCT is an aggressive, potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, and congenital immunodeficiency and autoimmune disorders.²  VOD is a rare complication of HSCT, which occurs in approximately 9-14% of HSCT patients.^3,4  Hepatic VOD, also known as SOS, is an early and life-threatening complication affecting the sinusoidal endothelial cells of the liver, which can typically occur within the first 21 days following HSCT.^4,5 Hepatic VOD progresses to multi-organ dysfunction in approximately 30-50% of cases.⁵  VOD with multi-organ dysfunction (MOD) is associated with an overall mortality (death) rate of 84%.³  MOD is characterized by the presence of renal or pulmonary dysfunction.^6,7  VOD is often characterized by sudden weight gain, hepatomegaly (abnormally enlarged liver), and elevated bilirubin.^6,7 

About Erwinaze
Erwinaze® (asparaginase Erwinia chrysanthemi) is currently approved in the U.S. for administration via intramuscular injection or via intravenous infusion in conjunction with chemotherapy.  It is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.⁸  Erwinaze is derived from the bacterium Erwinia chrysanthemi and is therefore immunologically distinct from E. coli-derived asparaginase and suitable for patients with hypersensitivity to E. coli-derived treatments⁹.  Outside of the U.S., Erwinaze is sold under the name Erwinase®. Please consult local labeling for product information specific to your country.

Erwinaze is contraindicated in patients who have had serious allergic reactions to Erwinaze, or had serious swelling of the pancreas, serious blood clots, or serious bleeding with past L-asparaginase treatment.  Erwinaze should be discontinued if any of the following occur: serious allergic reactions, including a feeling of tightness in the throat, unusual swelling/redness in the throat and/or tongue, or trouble bleeding; or severe inflammation of the pancreas. Glucose intolerance has been reported, which in some cases may be irreversible.  If blood clots of bleeding occur, discontinue Erwinaze until symptoms resolve. The most common side effects of Erwinaze are allergic reactions, too much sugar in the blood, fever, swelling of the pancreas, local reactions (swelling, rash, etc. where the needle entered the skin), vomiting, nausea, blood clots, liver problems, stomach pain/discomfort, and diarrhea. Please see full Prescribing Information for Erwinaze.  (https://www.jazzpharma.com/wp-content/uploads/2016/01/erwinaze-en-PI.pdf)

About Vyxeos (CPX-351)
CPX-351 (cytarabine and daunorubicin liposome injection) is an investigational product being evaluated for the treatment of AML and is a combination of cytarabine and daunorubicin encapsulated within a nano-scale liposome at a 5:1 molar ratio.  The proposed trade name, Vyxeos™, is conditionally approved by the FDA and is subject to confirmation upon approval of the NDA.  CPX-351 was granted orphan drug status by the FDA and the European Commission for the treatment of acute myeloid leukemia.  CPX-351 was granted Breakthrough Therapy Designation for the treatment of adults with therapy-related AML or AML with myelodysplasia-related changes and was also granted Fast Track designation by the FDA for the treatment of older patients with secondary AML.  On October 3, 2016 Jazz announced the initiation of a rolling submission of a New Drug Application (NDA) to the FDA, seeking marketing approval of CPX-351 for the treatment of AML. 

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a rapidly progressing and life-threatening blood cancer that rises in frequency with age.¹⁶  The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016.¹⁰  In the European Union, the number of new cases is estimated to be 20,100 in 2016.¹¹ 

The median age at diagnosis is 67 and with rising age there is progressive worsening of prognosis.^10,12  Advancing age is associated with increasing risk of specific chromosomal/mutational changes and risk of pre-malignant marrow disorders which give rise to more aggressive and less responsive forms of AML.^13,14  As patients age there is also reduced tolerance for intensive chemotherapy.¹⁵  As a consequence, advances in supportive care, intensive chemotherapy, and bone marrow transplantation have primarily benefitted younger patients with approximately one third of patients 18-60 years of age achieving cure.^13,15  Older patients have not achieved higher rates of cure or improved upon a 5-year survival rate of 10-20% in spite of 40 years of research.^15,16

About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is an international biopharmaceutical company focused on improving patients' lives by identifying, developing and commercializing meaningful products that address unmet medical needs. The company has a diverse portfolio of products and product candidates, with a focus in the areas of sleep and hematology/oncology.  In these areas, Jazz Pharmaceuticals markets Xyrem® (sodium oxybate) oral solution, Erwinaze® (asparaginase Erwinia chrysanthemi) and Defitelio® (defibrotide sodium) in the U.S. and markets Erwinase® and Defitelio® (defibrotide) in countries outside the U.S.  For more information, please visit www.jazzpharmaceuticals.com.

References:
1 Defitelio (defibrotide sodium) [package insert]. Palo Alto, CA: Jazz Pharmaceuticals; March 30, 2016.
2 Ikehara S. New strategies for BMT and organ transplantation. Int J Hematol. 2002;76(Suppl 1):161-4.
3 Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157-168.
4 Tsirigotis PD, Resnick IB, Avni B, et al. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen. Bone Marrow Transplant. 2014;49(11):1389-1392.
5 Carreras E, Díaz-Beyá M, Rosiñol L, et al. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood MarrowTransplant. 2011;17(11):1713-1720.
6 Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Brit J Haematol.  2015 Feb.; 168 (4); 481-91.
7 Mohty M, Malard F, Abecassis M, et al. Sinusoidal obstruction syndrome/veno‐occlusive disease: current situation and perspectives—a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015;50(6):781‐789.
8 Erwinaze^® (asparaginase Erwinia chrysanthemi) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals, Inc., December 2014.
9 Pieters R, Hunger SP, Boos J, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011 Jan 15; 117(2): 238–249.
10 American Cancer Society. Leukemia--Acute Myeloid (Myelogenous). Detailed Guide. What are the key statistics about acute myeloid leukemia? http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-key-statistics. Last revised February 22, 2016. Accessed November 3, 2016.
11 Decisions Research Group. Acute Myeloid Leukemia. https://decisionresourcesgroup.com/report/141439-biopharma-acute-myeloid-leukemia/.  Published November 2015. Accessed November 3, 2016.
12 Baer M, George S, Sanford B, et al. Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720. Leukemia. 2011;25(5):10.1038/leu.2011.9. doi:10.1038/leu.2011.9.
13 Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013 Feb 9;381(9865):484-495.
14 Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-474.
15 Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2004:98-117.
16  Kadia TM, Ravandi F, Cortes J, Kantarjian H. New drugs in acute myeloid leukemia. Ann Oncol. 2016 May;27(5):770-778.

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