Gloucester Pharmaceuticals Presents ISTODAX Data Demonstrating Clinical Benefit in Patients with CTCL Including Blood Involvement at ASH Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 6, 2009 - Gloucester Pharmaceuticals announced today the presentation of positive data from an analysis of ISTODAX® (romidepsin) in a subset of patients from Gloucester's registration study in cutaneous T-cell lymphoma (CTCL) at the 51st American Society of Hematology (ASH) Annual Meeting being held in New Orleans, LA. This analysis is an assessment of patients with CTCL who—in addition to skin disease and potential lymph node and visceral involvement—also had blood involvement. Blood involvement is characterized as having greater than five percent circulating Sézary (malignant) cells and is typically associated with advanced stage, aggressive disease. ISTODAX is a member of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors and was recently approved by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy.


 

“CTCL that includes blood involvement represents a major therapeutic challenge and the results of this analysis suggest that ISTODAX may help address a treatment void for these patients,” said Dr. Youn Kim, an investigator in studies of ISTODAX and Professor, Department of Dermatology and Director, Multidisciplinary Cutaneous Lymphoma Program, Stanford Cancer Center, Stanford, CA. “In this subset of 37 patients with blood involvement, the response rate is consistent with the response rate from the overall population of 96 patients in the registration trial. Additionally, the rapid and sustained reduction in Sézary counts observed in many patients with a higher blood tumor burden, which is typically associated with advanced stage, more aggressive disease, is noteworthy."


 

The results were described in a poster presentation entitled, “Clinically Significant Responses Achieved with Romidepsin in 37 Patients with Cutaneous T-Cell Lymphoma (CTCL) with Blood Involvement.” Of the 96 patients enrolled in the registration study, 37 patients had blood involvement. In this subset of patients with blood involvement (n=37), the response rate was 32% by overall composite assessment and included 2 (5%) confirmed complete responses. In the overall study population (n=96), the response rate was 34% and included 6 (6%) confirmed complete responses. The composite assessment included measurement of skin, lymph node and visceral involvement in addition to measurement of circulating malignant T-cells (Sézary cells). The median duration of response in the 37 patients with blood involvement has not been reached; however, the current maximum duration of response is 20 months. Pruritus, intense itching, was measured in these patients using a 100mm visual analog scale (VAS). 14 of 24 patients (58%) with moderate to severe pruritus at baseline (‰¥30 mm VAS) had a clinically meaningful decrease (‰¥30 mm) in VAS. The safety profile in this subset of 37 patients was similar to the overall safety profile of ISTODAX in the registration study which was characterized principally by mild (grade 1 and 2) gastrointestinal disturbances, hematologic toxicities, clinical chemistry abnormalities and asthenic conditions. The only study-drug related serious adverse event occurring in more than one patient was tumor lysis syndrome (2 patients).


 

“We're pleased to see that the results in this subset of patients with more challenging disease are similar to those observed overall in the registration study,” commented Jean Nichols, President and Chief Operating Officer of Gloucester Pharmaceuticals. “These data demonstrate that ISTODAX has the potential to provide sustained clinical benefit to patients with CTCL with blood involvement who have received at least one prior systemic therapy. In addition, the observed improvements in pruritus are encouraging because pruritus can be a particularly troubling symptom for this patient population."


 

About ISTODAX®


 

ISTODAX, a novel histone deacetylase (HDAC) inhibitor, has been approved by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. For full prescribing information, please visit www.ISTODAX.com. Gloucester is currently conducting a registration trial in peripheral T-cell lymphoma (PTCL) and additional studies of ISTODAX are being conducted in other hematologic and solid tumors. ISTODAX is not approved for the treatment of PTCL or other indications.


 

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 anemia; therefore, these hematological 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 fetus.


 

ISTODAX binds to estrogen receptors. Women of childbearing potential should be advised that ISTODAX may reduce the effectiveness of estrogen-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%), anemia (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, edema, 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.


 

For additional important safety information, please see full prescribing information for ISTODAX at www.ISTODAX.com or call 1-866-223-7145.


 

About Gloucester Pharmaceuticals


 

Gloucester Pharmaceuticals acquires clinical-stage oncology drug candidates and advances them through regulatory approval and commercialization. The Company's first candidate, ISTODAX® (romidepsin), a novel histone deacetylase (HDAC) inhibitor, is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. Gloucester is currently conducting a registration trial in peripheral T-cell lymphoma (PTCL) and anticipates data from this study in 2010. In addition, the Company is continuing further investigation of ISTODAX in other hematologic indications and solid tumors. For more information, please visit www.gloucesterpharma.com.


 

 


 

Contact: MacDougall Biomedical Communications

Sarah Cavanaugh/Cory Tromblee, 781-235-3060

scavanaugh@macbiocom.com

ctromblee@macbiocom.com


 

 

Posted: December 2009

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