FDA Approves Istodax for Peripheral T-Cell Lymphoma
FDA Grants Accelerated Approval of Istodax As Treatment for Patients with Peripheral T-Cell Lymphoma Who Have Received at Least One Prior Therapy
SUMMIT, N.J.--(BUSINESS WIRE)--Jun 17, 2011 - Celgene Corporation today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for its Supplemental New Drug Application (sNDA) for an additional indication for Istodax (romidepsin) for injection for the treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. Istodax is also approved for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
The PTCL approval was based on a priority (6 month) review by the FDA. Priority reviews are reserved for serious and life-threatening conditions that have an unmet medical need.
The Istodax sNDA approval is based upon results from two studies, a Phase II, multicenter, international, open-label, single-arm study of Istodax in patients with PTCL who had failed at least one prior systemic therapy (Study 3), which was presented at the 2010 American Society of Hematology annual meeting, and a single-arm clinical study of Istodax in patients with PTCL who had failed prior therapy (Study 4).
Istodax (romidepsin) for injection is an epigenetic therapy and a member of a class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. In vitro, Istodax causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines. The mechanism of the antineoplastic effect of romidepsin observed in nonclinical and clinical studies has not been fully characterized. For full prescribing information, visit www.istodax.com.
Istodax (romidepsin) for injection is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
Istodax (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.
These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
Important Safety Information
WARNINGS AND PRECAUTIONS:
- Treatment with Istodax has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with Istodax and modify the dose as necessary
- Serious and sometimes fatal infections have been reported during treatment and within 30 days after treatment with Istodax and the risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy.
- Electrocardiographic (ECG) changes have been observed with Istodax
- In patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment
- Due to the risk of QT prolongation, ensure that potassium and magnesium are within the normal range before administration
- Tumor lysis syndrome has been reported during treatment with Istodax. Patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken, and treatment should be instituted as appropriate
- Based on its mechanism of action, Istodax may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking Istodax, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D)
- Istodax binds to estrogen receptors. Advise women of childbearing potential that Istodax may reduce the effectiveness of estrogen-containing contraceptives
Peripheral T-Cell Lymphoma
- The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 3 (n=131) were thrombocytopenia (24%), neutropenia (20%), anemia (11%), asthenia/fatigue (8%), and leukopenia (6%), and in Study 4 (n=47) were neutropenia (47%), leukopenia (45%), thrombocytopenia (36%), anemia (28%), asthenia/fatigue (19%), pyrexia (17%), vomiting (9%), and nausea (6%).
- Infections were the most common type of serious adverse event reported in Study 3 (n=131) and Study 4 (n=47). In Study 3, 25 patients (19%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections.
- The most common adverse reactions regardless of causality in Study 3 (n=131) were nausea (59%), asthenia/fatigue (55%), thrombocytopenia (41%), vomiting (39%), diarrhea (36%), and pyrexia (35%), and in Study 4 (n=47) were asthenia/fatigue (77%), nausea (75%), thrombocytopenia (72%), neutropenia (66%), anemia (62%), leukopenia (55%), pyrexia (47%), anorexia (45%), vomiting (40%), constipation (40%), and diarrhea (36%).
Cutaneous T-Cell Lymphoma
- The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 1 (n=102) were infections (11%) and asthenia/fatigue (8%), and in Study 2 (n=83) were lymphopenia (37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).
- Infections were the most common type of serious adverse event reported in both Study 1 (n=102) and Study 2 (n=83) with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection.
- The most common adverse reactions regardless of causality in Study 1 (n=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%) and in Study 2 (n=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), lymphopenia (57%), infections (54%), anorexia (54%), vomiting (52%), hypocalcemia (52%), hyperglycemia (51%), hypoalbuminemia (48%), leukopenia (46%), dysgeusia (40%), and constipation (39%).
- Istodax is metabolized by CYP3A4. Avoid concomitant use with strong CYP3A4 inhibitors and potent CYP3A4 inducers if possible
- Caution should also be exercised with concomitant use of moderate CYP3A4 inhibitors and P-glycoprotein (P-gp, ABCB1) inhibitors
- Physicians should carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered Istodax and warfarin sodium derivatives
USE IN SPECIFIC POPULATIONS:
- Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Istodax, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
- Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution
Please see full Prescribing Information, including WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.
Istodax (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
Peripheral T-cell lymphoma comprises a heterogeneous group of malignancies of T-cell origin that account for about 10-15% of all cases of non-Hodgkin's lymphoma. PTCL can occur from young adulthood to old age and is slightly more common in men than in women. It is a particularly aggressive form of lymphoma with a short median duration of survival (approximately two years) from diagnosis.
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the company's Web site at www.celgene.com.
This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as 10K, 10Q and 8K reports.
Contact: Celgene Corporation
Jacqualyn A. Fouse, 908-673-9956
Sr. Vice President and
Chief Financial Officer
Brian Gill, 908-673-9530
Posted: June 2011
- FDA Approves Gloucester Pharmaceuticals' Istodax for Patients with Cutaneous T-cell Lymphoma - November 6, 2009
- FDA Advisory Committee Recommends Gloucester Pharmaceuticals' Romidepsin for Approval for Cutaneous T-cell Lymphoma - September 2, 2009
- Gloucester Pharmaceuticals Announces FDA Advisory Committee Meeting to Discuss Romidepsin New Drug Application - August 18, 2009