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Gloucester Pharmaceuticals Announces Positive Results From Phase 2b Registration Trial of Romidepsin in Refractory CTCL

Posted on: Monday, 19 May 2008, 12:00 CDT

Gloucester Pharmaceuticals today announced the presentation of positive data from a Phase 2b registration trial of romidepsin in patients with advanced cutaneous T-cell lymphoma (CTCL). The results were presented at the International Investigative Dermatology (IID) meeting in Kyoto, Japan, May 14-17, 2008. Romidepsin is a novel, cyclic peptide, pan-HDAC inhibitor under investigation for hematologic malignancies.

The primary endpoint of the registration trial, objective disease response rate (ORR) in patients who had failed previous therapy, was successfully achieved with an ORR of 40.3% (29/72 of evaluable patients). 33.3% (24/72) of patients experienced a partial response (PR) and 6.9% (5/72) of patients achieved a complete response (CR). Additionally, 92% (48/52) of patients with pruritus (intense itching) at the outset of the trial had some relief from their pruritus. Secondary endpoints, including duration of response, time to response and time to progression, continue to mature and will be presented at a future medical meeting.

"These data support the potential benefit for patients treated with romidepsin who suffer from various forms of CTCL. In particular, these results compare favorably with outcomes from the earlier Phase 2 NCI trial of romidepsin in CTCL," commented Dr. Sean Whittaker, Head of Dermatooncology Guys and St Thomas Hospital, London, England. "Further, I am encouraged by the appearance of durable responses in this patient population."

"We are indebted to the investigators and their patients who participated in this successful study," said Alan Colowick, MD, MPH, Chief Executive Officer of Gloucester Pharmaceuticals. "The positive outcome of this registration study reinforces our commitment to submit for US marketing approval of romidepsin in patients with CTCL later this year."

The results from the GPI-04-0001 trial were given in a presentation entitled Romidepsin Activity and Clinical Benefit in Refractory CTCL: Results from an International Multicenter Study by Dr. Sean Whittaker, et al. on May 16th at the International Investigative Dermatology meeting.

Safety and Tolerability

Ninety-six patients received at least one dose of romidepsin and were evaluable for safety Patients in GPI-04-0001 experienced adverse events (AEs) consistent with those seen in previous trials of romidepsin. The most common AEs include nausea, fatigue and vomiting. 22% (21/96) of patients experienced serious adverse events (SAEs) including disease progression (6%, 6/96), pyrexia (3%, 3/96) and sepsis, hypotension and tumor lysis syndrome (2%, 2/96 each).Overall, only 15% (14/96) patients discontinued due to a treatment-related AE.

About the Romidepsin CTCL Registration Trial

GPI-04-0001 is a Phase 2b, non-randomized, open-label, single-arm international, multi-center registration study designed to evaluate the efficacy, safety and tolerability of romidepsin as a treatment for cutaneous T-cell lymphoma (CTCL). This trial is being conducted under a special protocol assessment (SPA). The primary endpoint of the study is overall response rate. Secondary endpoints include disease control rate, duration of response, time to response and time to progression. Study patients receive romidepsin at a dose of 14 mg/m(2) intravenously on days 1, 8 and 15 of each 28-day cycle. Study treatment is 6 cycles although patients who show an objective response or stable disease may continue to receive therapy, at the discretion of the investigator and patient.

About CTCL

CTCL is a group of diseases, including mycosis fungoides and Sezary syndrome, both constitute types of non-Hodgkin's lymphoma in which certain cells of the lymph system (T cells) become cancerous and affect the skin and can affect other organs. The disorder is characterized by abnormal accumulation of malignant T cells in the skin, which result in the development of pruritus (intense itching), plaques and tumors. Occasionally malignant cells can be found circulating in the bloodstream and visceral (internal organ) involvement can occur. Symptoms of the disorder often include pruritus, an intense itching sensation, which leads to scratching that may cause breaks in the skin that lead to infection. In some patients, pruritus can be so severe that it affects overall quality of life. There are approximately 16,000 to 20,000 patients with CTCL in the United States and each year approximately 2,000 patients are newly diagnosed with the disease.

About Romidepsin

Romidepsin is a late-stage oncology drug candidate that is active across a broad range of hematological malignancies. A registration trial in cutaneous T-cell lymphoma (CTCL) has recently been completed, successfully meeting its primary endpoint based on overall response rate. A registration trial in a second indication, peripheral T-cell lymphoma (PTCL), is currently enrolling patients. Complete and durable responses were observed in a previous National Cancer Institute trial in PTCL. Numerous other trials are ongoing in additional indications including multiple myeloma. Over 600 patients to date have received romidepsin in clinical trials with the most common adverse effects including nausea, fatigue and vomiting. The cyclic peptide structure of romidepsin is unique among members of a new class of cancer drugs known as histone deacetylase, or HDAC, inhibitors. HDAC inhibition has been shown to increase acetylation of histones and other proteins, which is associated with anti-tumor activity including chromatin remodeling, tumor suppressor gene transcription, growth inhibition, and apoptosis. Preclinical studies suggest that romidepsin is among the most potent inhibitors of both Class I and Class II HDACs. Gloucester Pharmaceuticals retains worldwide rights to romidepsin which received Orphan Drug Designation from the FDA for the treatment of non-Hodgkin T-cell lymphomas, including CTCL and PTCL and Orphan status from the EMEA for the treatment of both CTCL and PTCL. The FDA has also granted Fast Track status for CTCL and PTCL. An NDA submission for romidepsin in CTCL is anticipated in 2008 and an MAA submission is projected for 2009.

About Gloucester Pharmaceuticals

Gloucester Pharmaceuticals acquires clinical-stage oncology drug candidates and advances them through regulatory approval and commercialization. The Company's first candidate, romidepsin, a novel HDAC inhibitor, is in late-stage development for T-cell lymphomas and has shown activity across a broad range of hematological malignancies. Gloucester has completed a registration trial of romidepsin in patients with cutaneous T-cell lymphoma (CTCL) and expects to submit applications for marketing approval in the US in 2008 and the EU in 2009. The Company is also enrolling patients in a registration trial for peripheral T-cell lymphoma (PTCL) and is evaluating romidepsin in multiple additional indications including multiple myeloma. For more information, please visit www.gloucesterpharma.com.

Source: Business Wire

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