Jazz Pharmaceuticals Initiates Rolling NDA Submission For Defibrotide For The Treatment Of Severe Hepatic Veno-Occlusive Disease

DUBLIN -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced the initiation of a rolling submission of a New Drug Application (NDA) to the United States (U.S.) Food and Drug Administration (FDA) for defibrotide for the treatment of severe hepatic veno-occlusive disease (VOD) in patients undergoing hematopoietic stem-cell transplantation (HSCT) therapy.  Defibrotide has been granted Fast Track Designation to treat severe VOD by the FDA.

"Our start of the NDA submission for defibrotide marks an important step forward in our efforts to provide a treatment option for patients in the U.S. who develop this rare, life-threatening complication of HSCT," said Jeffrey Tobias, M.D., executive vice president and chief medical officer of Jazz Pharmaceuticals.  "We expect to complete the submission of the NDA in the first half of 2015, at which time we will be requesting a Priority Review of the application, and we will continue to work closely with the FDA as we seek approval of the NDA.  As part of our commitment to ensure that eligible patients have access to defibrotide as we pursue U.S. approval, we will continue to provide patients access to defibrotide through an expanded access treatment protocol that is open under an ongoing investigational new drug application in the U.S."

The Fast Track Designation is designed to facilitate the development and expedite the review of drugs that treat serious, life-threatening conditions and that address unmet medical needs.  The Fast Track process allows a company to submit individual sections of its NDA for review by the FDA as they are completed rather than waiting until the entire application is complete before it can be submitted and reviewed.

Earlier this year, Jazz Pharmaceuticals acquired the rights to defibrotide in the U.S. and other markets in North America, South America and Central America.  Jazz Pharmaceuticals markets defibrotide in Europe under the name Defitelio®▼ (defibrotide).  Defitelio is the first and only licensed product in Europe for the treatment of severe hepatic VOD in patients over one month of age undergoing HSCT therapy.

About VOD

Veno-occlusive disease (VOD) is an early complication in patients undergoing HSCT therapy.  In its severe form, VOD can be life-threatening and is associated with multi-organ failure; it is fatal in over 80% of patients.1,2  HSCTs are performed with curative intent in patients with hematological malignancies, selected solid tumors and some non-malignant disorders, such as serious hemoglobinopathies.3,4   In the U.S., defibrotide was granted Orphan Drug Designation to treat and prevent VOD by the FDA in May 2003.

About Defibrotide
In October 2013, the European Commission granted marketing authorization under exceptional circumstances for Defitelio®▼ (defibrotide) for the treatment of severe hepatic VOD in patients undergoing HSCT therapy.  It is indicated in patients over one month of age.  Defitelio is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy.

Please consult the Defitelio Summary of Product Characteristics (SmPC) [http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/human/medicines/002393/human_med_001646.jsp] before prescribing, particularly in relation to use of medicinal products that increase the risk of hemorrhage, concomitant systemic anticoagulant therapy, medicinal products that affect platelet aggregation, use in patients who have or develop clinically significant acute bleeding requiring blood transfusion, and patients who have hemodynamic instability.

The most frequent adverse events observed during pre-marketing use were hemorrhage, hypotension and coagulopathy.5   Please also consult the Defitelio SmPC for the full list of all side effects reported with Defitelio.

▼ 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 theSmPC.

About Jazz Pharmaceuticals plc

Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a specialty biopharmaceutical company focused on improving patients' lives by identifying, developing and commercializing differentiated products that address unmet medical needs.  The company has a diverse portfolio of products and/or product candidates in the areas of sleep, hematology/oncology, pain and psychiatry.  The company's U.S. marketed products in these areas include: Xyrem® (sodium oxybate) oral solution, Erwinaze® (asparaginase Erwinia chrysanthemi), Prialt® (ziconotide) intrathecal infusion, Versacloz® (clozapine) oral suspension, FazaClo® (clozapine, USP) HD and FazaClo LD.  Jazz Pharmaceuticals also has a number of products marketed outside the United States, including Erwinase® and Defitelio® (defibrotide). For more information, please visit www.jazzpharmaceuticals.com.

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995

This press release contains forward-looking statements, including, but not limited to, statements related to Jazz Pharmaceuticals' plans to complete a rolling NDA submission for defibrotide in the U.S. and the timing thereof, and other statements that are not historical facts.  These forward-looking statements are based on Jazz Pharmaceuticals' current expectations 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, the inherent uncertainty associated with the regulatory approval process, including the risks that the company may be required to conduct additional time-consuming and costly clinical trials prior to submission of the NDA or as a condition of regulatory approval of defibrotide in the U.S. and that the company may otherwise be unable to obtain or maintain any regulatory approval for defibrotide in the U.S., and those other risks detailed from time-to-time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including the Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and future filings and reports by the company.  Jazz Pharmaceuticals undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events or changes in its expectations.

1. Carreras E. EBMT-ESH Handbook 2012. Chapter 11: Early complications after HSCT. 
2. Coppell JA, et al. Biol Blood Marrow Transplant. 2010;16:157-168.
3. Tsakiris DA, Tichelli A. Best Pract Res Clin Haematol. 2009;22:137-145.
4. Majhail NS, et al. Bone Marrow Transplant. 2013;48:294-300.
5.  Defitelio® Summary of product characteristics, 2013. 

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