Celgene Corporation
Dec 5, 2010
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New Clinical Data Evaluating ISTODAX® in Pivotal Open-Label Phase II Study for Patients with Peripheral T-Cell Lymphoma (PTCL)

Study Reported Primary Endpoint Reached, as 13% of Patients Achieved a Complete Response

Median Duration of Response Was 12 Months

BOUDRY, Switzerland, Dec 05, 2010 (BUSINESS WIRE) --

Celgene International Sàrl (Nasdaq:CELG) today announced that data from a pivotal Phase II, multicenter, international, open-label study of romidepsin (ISTODAX®) in progressive or relapsed PTCL following prior systemic therapy were presented at the 52nd American Society of Hematology Annual Meeting.

In the study, patients with histopathologically confirmed PTCL who failed or were refractory to prior systemic therapy received 14 mg/m2 of ISTODAX as a four-hour infusion on days 1, 8 and 15 of a 28-day cycle for up to six cycles. Treatment could be extended for response or stable disease.

Of 130 patients with histopathologically confirmed PTCL in the study, the overall response rate was 26% (34/130), as assessed by an Independent Review Committee (IRC) using the International Workshop Criteria. Thirteen percent (17/130) of patients achieved a complete response - the primary endpoint of the study - and another 13% (17/130) achieved a partial response. The median duration of response for all patients who responded was 12 months (range 1-801+ days). The median duration of response for patients who achieved a complete response has not been reached (median duration of follow-up: 8.2 months), and 82% (14/17) of patients with a complete response had not progressed as of the data cut-off for the IRC evaluation (March 31, 2010).

Toxicities associated with ISTODAX® in the study were as follows: 96.2% (126/131) of patients evaluable for safety experienced at least one treatment-emergent adverse event, with the most common grade 3 or higher adverse events reported as thrombocytopenia (24% 31/131), neutropenia (20% 26/131), infections (17% 22/131) and anaemia (10% 13/131).

Romidepsin (ISTODAX) is not approved as a treatment in progressive or relapsed PTCL.

About ISTODAX

ISTODAX® (romidepsin) is a member of a new 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. HDAC inhibitors can be divided into four main classes: cyclic tetrapeptides (I), short-chain fatty acids (II), hydroxamic acids (III), and benzamides (IV). The cyclic peptide structure of ISTODAX is novel among the cyclic tetrapeptides. In vitro, ISTODAX causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines. For full prescribing information, visit www.ISTODAX.com.

ISTODAX is approved in the United States for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

Important Safety Information

ISTODAX is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

Warnings and Precautions

Due to the risk of QT prolongation, potassium and magnesium should be within the normal range before administration of ISTODAX.

Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anaemia; therefore, these haematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary.

Several treatment-emergent morphological changes in ECGs including T-wave and ST-segment changes have been reported in clinical studies. The clinical significance of these changes is unknown. In patients with congenital long QT syndrome, patients with 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, such as the monitoring of electrolytes and ECGs should be considered.

Based on its mechanism of action, ISTODAX may cause fetal harm. Woman should avoid becoming pregnant while being treated with ISTODAX and pregnant women should be advised of the potential harm to the foetus.

ISTODAX binds to oestrogen receptors. Women of childbearing potential should be advised that ISTODAX may reduce the effectiveness of oestrogen-containing contraceptives.

Adverse Reactions

Safety data was available and evaluated in 185 patients with CTCL in two clinical trials. Adverse reactions are presented separately for each study due to methodological differences between the studies. The most common reported adverse reactions in Study 1 were nausea (56%), fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%) and in Study 2 were nausea (86%), fatigue (77%), anaemia (72%), thrombocytopenia (65%), ECG T-wave changes (63%), neutropenia (57%), and lymphopenia (57%). Most of the adverse reactions were reported to be mild or moderate in severity. Most deaths in the studies were due to disease progression. Discontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Serious adverse reactions reported in > 2% of patients in Study 1 were infection, sepsis, and pyrexia. In Study 2, serious adverse reactions in > 2% of patients were infection, supraventricular arrhythmia, neutropenia, fatigue, oedema, central line infection, ventricular arrhythmia, nausea, pyrexia, leukopenia, and thrombocytopenia.

Drug Interactions

Prothrombin time (PT) and International Normalized Ratio (INR) should be carefully monitored in patients concurrently administered ISTODAX and Coumadin derivatives.

Co-administration of strong CYP3A4 inhibitors may increase concentrations of ISTODAX and should be avoided.

Co-administration of potent CYP3A4 inducers may decrease concentrations of ISTODAX and should be avoided.

Caution should be exercised if ISTODAX is administered with drugs that inhibit P-glycoprotein.

Use in Specific Patient Populations

Patients with moderate and severe hepatic impairment or end-stage renal disease should be treated with caution.

About PTCL

Peripheral T-cell lymphoma is a term that encompasses a number of different malignancies of T-cell origin that account for about 10-15% of all cases of non-Hodgkin's lymphoma. PTCL can occur at any age 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 life expectancy (approximately two years) from diagnosis.

About Celgene International Sàrl

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website 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.

SOURCE: Celgene International Sàrl

Celgene International Sàrl
Kevin Loth, +41 32 729 86 21
Director of External Relations