Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 2 Clinical Trial Evaluating Defibrotide for the Prevention of Acute Graft-versus-Host Disease
"Potential complications of hematopoietic stem cell transplant such as acute Graft-versus-Host Disease can be life threatening and even fatal," said
The Phase 2 clinical trial is a prospective, randomized, open-label study of the efficacy and safety of defibrotide added to standard of care immunoprophylaxis for the prevention of aGvHD, compared to the standard of care alone. Jazz expects to enroll approximately 150 adult and pediatric patients who have undergone allogeneic HSCT from an unrelated donor. The primary endpoint is cumulative incidence of Grade B-D aGvHD by day +100 post-allogeneic HSCT. Additional information about the trial, including eligibility criteria and a list of clinical trial sites can be found at: https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03339297).
This Phase 2 trial complements the company's ongoing Phase 3 clinical trial evaluating defibrotide for prevention of hepatic veno-occlusive disease (VOD) in high-risk adult and pediatric patients undergoing hematopoietic stem cell transplant.
Graft-versus-Host-Disease (GvHD) is a life-threatening complication of HSCT, a potentially curative option for several malignant and non-malignant disorders, and occurs when immune cells from a non-identical donor (graft) recognize the transplant recipient (host) as foreign. GvHD is the most frequent cause of morbidity and non-relapse mortality following allogeneic HSCT.1 One in five patients receiving a transplant from an unrelated donor dies from GvHD. Approximately 24,000 allogeneic patients in
About Defitelio® (defibrotide sodium)
In the U.S., Defitelio® (defibrotide sodium) injection 80mg/mL received U.S.
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
▼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)
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.6 VOD is a rare complication of HSCT that occurs in approximately 9-14% of HSCT patients.7,8 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.8,9 Hepatic VOD progresses to become life-threatening in approximately 30-50% of cases.9 VOD with multi-organ dysfunction (MOD), when left untreated, can be associated with an overall mortality (death) rate of 84%.7 MOD is characterized by the presence of renal or pulmonary dysfunction.10,11 VOD is often characterized by sudden weight gain, hepatomegaly (abnormally enlarged liver), and elevated bilirubin.10,11
"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 defibrotide as a potential treatment for the prevention of aGvHD in adult and pediatric patients after allogeneic HSCT 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: pharmaceutical product development and clinical success thereof; and the regulatory approval process; 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
- Pasquini MC,
Zhu X. Currentuse and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides, 2015. Available at: http://www.cibmtr.org
- Passweg JR, Baldomero H, Bader P, et al. Hematopoietic stem cell transplantation in
Europe2014: more than 4000 transplants annually. Bone Marrow Transplantation. 2016;51:786-92.
- Jagasia M, et al. Blood. 2012;119: 296-307.
- Jacobsohn DA, Bone Marrow Transplantation. 2008;41: 215-221.
- Rowlings PA, Przepiorka D, et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade.
British Journal of Haematology. 1997;97:855-64.
- Ikehara S. New strategies for BMT and organ transplantation. Int J Hematol. 2002;76(Suppl 1):161-4.
- 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.
- 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.
- 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.
- Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Brit J Haematol. 2015 Feb.; 168 (4); 481-91.
- 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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