FDA Approves Gloucester Pharmaceuticals` ISTODAX® for Patients with Cutaneous T-cell Lymphoma

Thu Nov 5, 2009 4:43pm EST

* Reuters is not responsible for the content in this press release.

--Overall response rates exceededprimary endpointin ISTODAX studies; sustained
duration of response reported--
CAMBRIDGE, Mass.--(Business Wire)--
Gloucester Pharmaceuticals announced today that the U.S. Food and Drug
Administration (FDA) approved ISTODAX® (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

"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/m2 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 ("Sézary 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 ≥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. 

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

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

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

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

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. 

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