Jazz Pharmaceuticals Announces U.S. FDA Acceptance for Filing with Priority Review of NDA for Defibrotide for Hepatic Veno-Occlusive Disease

DUBLIN, Sept. 30, 2015 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the United States (U.S.) Food and Drug Administration (FDA) has accepted for filing with Priority Review its recently submitted New Drug Application (NDA) for defibrotide.  Defibrotide is an investigational agent proposed for the treatment of patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with evidence of multi-organ dysfunction (MOD) following hematopoietic stem-cell transplantation (HSCT).  

Priority Review status is designated for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists.  Based on timelines established by the Prescription Drug User Fee Act (PDUFA), FDA review of the NDA is expected to be completed by March 31, 2016. 

"The FDA's acceptance for filing and Priority Review status of the NDA for defibrotide is an important milestone for Jazz and reflects our commitment to bringing meaningful medicines to patients who have significant unmet needs," said Karen Smith, M.D., Ph.D., Global Head of Research and Development and Chief Medical Officer of Jazz Pharmaceuticals.  "We look forward to continuing to work closely with the FDA to obtain approval for defibrotide for patients with hepatic VOD with evidence of MOD in the U.S. as quickly as possible, as there are no other approved therapies for treating this rare, often fatal complication of HSCT."

The NDA includes safety and efficacy data from three clinical studies of defibrotide for the treatment of hepatic VOD with MOD following HSCT, as well as a retrospective review of registry data from the Center for International Blood and Marrow Transplant Research.  The safety database includes over 900 patients exposed to defibrotide in the clinical development program for the treatment of hepatic VOD.

"We applaud the FDA for working with Jazz in accepting this application for a timely review as bone marrow transplant patients who develop VOD with MOD currently have no effective options for this potentially life-threatening syndrome," said Susan K. Stewart, Executive Director, BMT InfoNet (Blood & Marrow Transplant Information Network).

About VOD

HSCT is a potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, congenital immunodeficiencies and metabolic disorders.1  Hepatic VOD is a rare, early and life-threatening complication of HSCT. VOD in association with MOD has a mortality rate that exceeds 80%.2

About Defibrotide

In the U.S., defibrotide is an investigational drug for the treatment of patients with hepatic VOD with evidence of MOD following HSCT.  Defibrotide was granted Orphan Drug Designation by the FDA in May 2003 and has Fast Track designation.  Defibrotide is being made available as an investigational new drug (IND) free of charge through an expanded access Treatment Protocol.

The ongoing expanded access Treatment Protocol is currently enrolling patients diagnosed with VOD in the U.S.  Expanded access programs are part of an effort by the FDA and the pharmaceutical industry to make investigational drugs available for the treatment of serious or life threatening diseases in people with limited treatment options.  For information about the defibrotide study, contact Erin Tokunaga at [email protected] or Lam Calderon (1.312.706.6240; [email protected]); or visitwww.clinicaltrials.gov (Identifier: NCT00628498).

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 hepatic VOD in patients undergoing HSCT therapy.  It is the first and only approved treatment in Europe for severe hepatic 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.

Please consult the Defitelio Summary of Product Characteristics (SmPC) 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.  Please 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. (http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/human/medicines/002393/human_med_001646.jsp)

About Jazz Pharmaceuticals plc

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 and Erwinaze® (asparaginase Erwinia chrysanthemi) in the U.S., and markets Erwinase® and Defitelio® (defibrotide) in countries outside the U.S.  For more information, please visitwww.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 the expected timing of and efforts in connection with obtaining FDA approval of Jazz Pharmaceuticals' NDA for defibrotide and other statements that are not historical facts.  These forward-looking statements are based on the company's 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, among others, risks and uncertainties associated with the difficulty and uncertainty of pharmaceutical product development, including the timing thereof, and the uncertainty of clinical success; the inherent uncertainty associated with the regulatory approval process, including the risk that the company may be unable to obtain regulatory approval for defibrotide in the U.S. in a timely manner or at all; and other risks and uncertainties affecting the company, including those described 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 company's most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q and future filings and reports by the company.  Other risks and uncertainties of which the company is not currently aware may also affect the company's forward-looking statements and may cause actual results and 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 the company on its website or otherwise.  The company 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.

1Gratwohl A et al. JAMA 2010; 303:1617-1624 (Ikehara, 2002).
2Coppell et al. 2010, Carreras et al. 2011.