CAMBRIDGE, Mass. -- Gloucester Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) approved ISTODAX(R) (romidepsin) for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. The approval of ISTODAX was based on objective disease response defined as the proportion of patients with confirmed complete response or partial response. The New Drug Application (NDA) included efficacy data from two studies encompassing 167 patients. ISTODAX is a member of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors and is expected to be commercially available in January 2010.
"CTCL is a devastating cancer in which many patients suffer from disfiguring tumors, horribly itchy and infected skin and, in advanced stages, lesions in other organs," said Youn Kim, MD, an investigator in studies of ISTODAX and Professor, Department of Dermatology and Director, Multidisciplinary Cutaneous Lymphoma Program, Stanford Cancer Center, Stanford, CA. "Current systemic therapies have proved inadequate and patients with CTCL desperately need treatment options that can offer sustained relief from their disease so they can live fuller lives. ISTODAX meets a significant unmet need and provides hope for patients with CTCL, their families and their physicians."
Paul A. Bunn, Jr., MD, James Dudley Chair in Cancer Research, Professor and Director, University of Colorado Cancer Center and past-President of the American Society of Clinical Oncology said, "ISTODAX offers physicians an important new treatment choice that can provide clinically meaningful, and, most importantly, sustainable responses for some patients with CTCL who have failed prior systemic therapy. Additionally, the approval of a second HDAC inhibitor in cancer is very exciting and speaks to the potential for this class of compounds."
"The approval of ISTODAX is the result of an extraordinary commitment by our clinical investigators and the patients and their families who volunteered to participate in the ISTODAX clinical trials," said Jean Nichols, PhD, President and Chief Operating Officer of Gloucester Pharmaceuticals. "Gloucester would also like to recognize the National Cancer Institute which played an invaluable role in the development of ISTODAX."
Alan Colowick, MD, Chief Executive Officer of Gloucester Pharmaceuticals said, "The approval of ISTODAX is a tremendous accomplishment for Gloucester Pharmaceuticals and for the patients we serve. This milestone is also an important step in the continued clinical development path for ISTODAX in oncology. We look forward to presenting data from our registration study of ISTODAX in peripheral T-cell lymphoma in 2010 and continuing further investigation in additional hematologic indications and solid tumors."
About CTCL
CTCL is a type of non-Hodgkin's lymphoma, which is a cancer of the immune system. CTCL is caused by a mutation of T cells, unlike most non-Hodgkin's lymphomas which are generally of B-cell origin. The malignant T cells involve the skin, causing plaques, patches, erythroderma and/or tumors and can involve other organs, including the blood, lymph nodes and viscera.
Clinical Trials Overview
The ISTODAX approval was based upon two prospective multicenter, single-arm clinical studies in patients with CTCL. 167 patients with CTCL were accessed for efficacy in the United States, Europe and Australia. Study 1, sponsored by Gloucester, included 96 patients with confirmed CTCL after failure of at least 1 prior systemic therapy. Study 2, sponsored by the National Cancer Institute, included 71 patients with a primary diagnosis of CTCL who received at least 2 prior skin directed therapies or one or more systemic therapies. Patients were treated with ISTODAX at a starting dose of 14 mg/m(2 )infused over 4 hours on days 1, 8, and 15 every 28 days.
In both studies, patients could be treated until disease progression at the discretion of the investigator and local regulators. Objective disease response was evaluated according to a composite endpoint that included assessments of skin involvement, lymph node and visceral involvement, and abnormal circulating T-cells ("Sezary cells").
The primary efficacy endpoint for both studies was overall objective disease response rate (ORR) based on the investigator assessments and defined as the proportion of patients with confirmed complete response (CR) or partial response (PR). CR was defined as no evidence of disease and PR as greater-than or equal to 50% improvement in disease. Secondary endpoints in both studies included duration of response and time to response.
The ORRs in these two trials were similar (34% and 35% in Study 1 and Study 2, respectively) and CR rates were the same (6%). The median response duration was 15 months (range of 1 to 20+ months) in Study 1 and 11 months (range of 1 to 66+ months) in Study 2. Median time to first response was 2 months (range 1 to 6) in both studies. Median time to CR was 6 months in Study 1 and 4 months in Study 2 (range 2 to 9).The most common adverse reactions in Study 1 were nausea, fatigue, infections, vomiting and anorexia and in Study 2 were nausea, fatigue, anemia, thrombocytopenia, ECG T-wave changes, neutropenia and lymphopenia. See below for important safety information.
In Study 1, the median number of prior skin-directed therapies was 2 and the median number of prior systemic therapies was 2. In Study 2, the median number of prior skin-directed therapies was 1 and the median number of prior systemic therapies was 2. In Study 1, 71% of the patients had Stage IIB or greater disease and 87% of the patients in Study 2 had Stage IIB or greater disease.
Copyright 2009, Gloucester Pharmaceuticals
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