June 17, 2008
Gloucester Pharmaceuticals Announces Phase 2 Data for Romidepsin Showing Durable Response in Refractory CTCL
Gloucester Pharmaceuticals today announced that positive data from a Phase 2 trial of romidepsin conducted by the U.S. National Cancer Institute (NCI) were presented at the 13th Congress of the European Hematology Association in Copenhagen, Denmark. Romidepsin is a novel, cyclic peptide, pan-HDAC inhibitor under investigation for hematologic malignancies.
In a presentation entitled Romidepsin Induces Clinically Significant and Durable Responses in Relapsed or Refractory CTCL: A National Cancer Institute International, Multicenter Study at the 13th Congress of the European Hematology Association, Dr. Susan Bates of the U.S. National Cancer Institute and Principal Investigator described the results of the study. Overall, 39.7% of evaluable patients had a response, with an 11.1 month median duration of response.
The primary endpoints of the NCI trial were objective disease response rate (ORR), complete response rate (CR) and duration of response in patients who had failed previous therapy. The ORR was 39.7% (25/63 evaluable patients), 33.3% (21/63) of patients experienced a partial response (PR) and 6.3% (4/63) experienced a complete response (CR). The median duration of response was 11.1 months in patients experiencing PR or CR. Responses were observed at all stages of disease, including an ORR of 29.4% (10/34) in patients with Stage IV disease.
"The results indicate that many patients with refractory cutaneous T-cell lymphoma receiving romidepsin in the NCI study showed significant durability of response, a critical unmet need for patients with this disease," said Jean Nichols, Ph.D., President and Chief Operating Officer of Gloucester Pharmaceuticals. "We are also very encouraged that these data are consistent with and support the previously reported positive data from Gloucester's registration trial of romidepsin in patients with cutaneous T-cell lymphoma. The similarity in response rates is striking. Data from both studies will be submitted in a New Drug Application for romidepsin in cutaneous T-cell lymphoma later this year."
About the Romidepsin NCI CTCL Trial
NCI Study 1312 is a 7-arm, Phase 2, open-label trial of romidepsin in patients with CTCL and PTCL conducted at the NCI and 9 additional sites in the US and Australia. The study enrolled 71 CTCL patients in 3 arms of the study that received romidepsin. Patients received 14mg/m2 of romidepsin infused on days 1, 8 and 15 every 28 days.
Safety and Tolerability
Overall the adverse event profile was similar to that reported previously by the NCI for romidepsin. In this study, the most frequent adverse events of Grade 3 or higher included fatigue (14.1% Grade 3, 10/71 and 2.8% Grade 4, 2/71), reversible thrombocytopenia (14.1% Grade 3, 10/71 and 1.4% Grade 4, 1/71) and nausea (7% Grade 3, 5/71). 5 patients did not complete the study due to drug-related adverse events.
CTCL is a group of diseases, including mycosis fungoides and Sezary syndrome, which 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.
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 fatigue, gastrointestinal disturbances and generally mild to moderate bone marrow suppression. 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 a pan-HDAC inhibitor and 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 pan-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.