DUBLIN, Jan. 17, 2017 /PRNewswire/ -- Jazz
Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the
first patient has been enrolled in a Phase 3 clinical trial
comparing the efficacy and safety of defibrotide versus best
supportive care (BSC) in the prevention of hepatic veno-occlusive
disease (VOD) in adult and pediatric patients undergoing
hematopoietic stem cell transplant (HSCT) who are at high risk or
at very high risk of developing VOD. The defibrotide clinical
trial will be conducted across approximately 100 medical centers in
the United States (U.S.),
Canada, Asia Pacific and countries in the European
Union (EU).
"The initiation of this trial is another step forward
in Jazz's development program for defibrotide as a treatment
option for patients who are at high risk or very high
risk of developing this life-threatening condition," said
Karen Smith, M.D., Ph.D., global
head of research and development and chief medical officer of Jazz
Pharmaceuticals. "If the data from this trial are positive,
they may be used to pursue regulatory approval of a label expansion
for defibrotide in both the U.S. and EU to include the prevention
of hepatic VOD in high risk patients following HSCT."
The Phase 3 trial is a randomized, open-label, multi-center
trial with an adaptive design comparing the efficacy of defibrotide
vs. BSC in the prevention of hepatic VOD. The trial is
expected to enroll approximately 400 adult and pediatric patients
undergoing HSCT who are at high risk or very high risk of
developing VOD. High (or very high) risk patients are
identified due to the clinical regimen required to prepare them for
HSCT, as well as their prior medical history and concomitant
disease. The adaptive design allows for an interim analysis with
pre-defined stopping points for early success or failure as well as
the option to increase enrollment if needed to preserve the
statistical power of the trial.
For patients randomized to receive defibrotide prophylaxis,
defibrotide will be administered starting on the day before the
first day of the conditioning regimen for a recommended minimum of
21 days and ending no later than Day +30 post HSCT. The
primary endpoint is VOD-free survival at Day +30 post-HSCT.
Additional information about the trial, including eligibility
criteria and a list of clinical trial sites can be found at:
www.clinicaltrials.gov (ClinicalTrials.gov Identifier:
NCT02851407).
About Defitelio® (defibrotide
sodium)1
Defibrotide has orphan drug designation
from the U.S. Food and Drug Administration (FDA) and European
Medicines Agency (EMA) for the prevention of hepatic VOD. In
the U.S. Defitelio® (defibrotide sodium) injection 80mg/mL received
U.S. 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.
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 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.
"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 potential of defibrotide as a
treatment for the prevention of VOD in adult and pediatric patients
undergoing HSCT who are at high risk or very high risk of
developing VOD, the potential for label expansion 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, without limitation, risks and uncertainties associated
with of pharmaceutical product development and clinical success
thereof, the uncertainty of regulatory approval, and other risks
and uncertainties affecting the company and its development
programs, 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
Quarterly Report on Form 10-Q for the quarter ended September
30, 2016 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 the 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.
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.
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