Gloucester Pharmaceuticals Presents Positive Clinical Data for Romidepsin in CTCL and Further Preclinical Evidence of Synergism with Bortezomib at ASCO
--Pooled Analysis Supports Clinical Activity in CTCL--
--Preclinical Combination Data in Mantle Cell Lymphoma Adds to Data in Other Hematologic Malignancies--
Cambridge, MA - June 1, 2009 - Gloucester Pharmaceuticals today announced presentations of two studies of romidepsin, its novel, cyclic peptide, histone deacetylase inhibitor under investigation for the treatment of hematologic malignancies at the 45th annual American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida. The first presentation was of clinical results from a pooled analysis of two Phase 2 international studies of romidepsin in patients with cutaneous T-cell lymphoma (CTCL) and the second was data from a preclinical study of romidepsin in combination with Velcade® (bortezomib) in mantle cell lymphoma (MCL).
Marie-France Demierre, M.D., of the Boston Medical Center in Boston, Massachusetts presented a poster entitled Pooled Analyses of 2 International, Multicenter Clinical Studies of Romidepsin in 167 Patients with Cutaneous T-Cell Lymphoma. This combined analysis included results from Gloucester's Phase 2b registration trial and a supportive Phase 2 study which was sponsored by the NCI under a Cooperative Research and Development Agreement (CRADA) with Gloucester. In this analysis, evaluable patients with refractory CTCL who received romidepsin had an overall response rate of 41% (55/135). Ten (7%) evaluable patients achieved a complete response and 45 (33%) achieved a partial response. Responses were observed at all stages of disease, including an overall response rate of 42% in evaluable patients with Stage IIB or greater disease, including patients with Sézary syndrome. A sustained duration of response was observed with a median of 14.9 months.
Importantly, in an analysis of pruritus relief conducted in the registration study, which excluded patients currently on steroid or antihistamine treatment, most (63%) patients with moderate to severe pruritus at baseline experienced significant pruritus relief, a key indicator of clinical benefit.
Overall, the most common drug-related adverse events (AEs) in treated patients (n=167) were mild (Grade 1-2) and included nausea (67%), fatigue (49%), vomiting (34%), anorexia (34%), thrombocytopenia (32%), and anemia (31%). The only drug‑related serious adverse event (SAE), occurring in >2% of patients, was fatigue (5 patients; 3%).
"These trials generated impressive results - including an overall response rate of 41% among evaluable patients in the combined data as well as encouraging complete response and sustained duration of response in refractory patients and a significant decrease in pruritus," Said Marie-France Demierre, M.D., of the Boston Medical Center in Boston, Massachusetts and an investigator in Gloucester's registration study. "It is also encouraging to see that a significant proportion of advanced patients responded to the treatment, including among the 19 Sézary patients, 58% of whom responded. These findings suggest that romidepsin may be able to arrest CTCL progression for patients at all stages of disease."
The data from two clinical studies that comprise the pooled analysis are included in the New Drug Application submission for romidepsin in CTCL, which has been accepted for review by the Food and Drug Administration. "We look forward to working with the FDA as they review our application," stated Jean Nichols, Ph.D., President and COO of Gloucester. In addition, a single-agent registration study of romidepsin in patients with PTCL and a Phase 2 study of romidepsin in combination with Velcade® in patients with multiple myeloma are actively enrolling."
In a separate preclinical study, researchers at Herbert Irving Comprehensive Cancer Center at New York-Presbyterian Hospital and Columbia University Medical Center demonstrated that the combination of romidepsin with bortezomib (Velcade®) is highly synergistic in models of mantle cell lymphoma (MCL), a subtype of non-Hodgkin's lymphoma with poor prognosis. These results support ongoing Phase 1 and Phase 1/2 studies of romidepsin in combination with bortezomib in patients with multiple myeloma and suggest that further studies to explore the use of romidepsin in combination with bortezomib for MCL and other hematological malignancies may be warranted.
"Based on the promising synergy observed in these preclinical investigations, we look forward to further evaluation of the romidepsin and Velcade® combination in both T and B cell lymphomas as well as multiple myeloma," commented Owen O'Connor, M.D., director of the Lymphoid Development and Malignancy Program and chief of the Lymphoma Service at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian Hospital/Columbia University Medical Center and principal investigator of the of the laboratory that performed the work.
"We are very enthusiastic to see that romidepsin continues to generate positive results across a spectrum of hematologic malignancies and we look forward to reviewing results in PTCL and multiple myeloma, while exploring the potential of romidepsin in combination with Velcade and other targeted therapies," stated Alan Colowick, M.D., M.P.H., CEO of Gloucester.
About Romidepsin
Romidepsin is a late-stage oncology drug candidate being studied across a range of hematologic malignancies. A registration trial in cutaneous T-cell lymphoma (CTCL) has been completed, successfully exceeding 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 sustainable responses were observed in a previous National Cancer Institute trial including both patients with CTCL and PTCL. Numerous other trials are ongoing in additional indications including multiple myeloma. Over 850 patients, to date, have received romidepsin in clinical trials with the most common adverse effects including fatigue, gastrointestinal disturbances and hematologic toxicities. Romidepsin's cyclic peptide structure is novel among members of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDAC inhibition has been shown to increase acetylation of histones and other proteins. The downstream effects of HDAC inhibition include growth inhibition, apoptosis, inhibition of angiogenesis and differentiation. Preclinical studies suggest that romidepsin is a pan-HDAC inhibitor and is a potent inhibitor of Class I, Class II and Class IV HDACs. Gloucester Pharmaceuticals retains worldwide rights to romidepsin which received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of non-Hodgkin's T-cell lymphomas, including CTCL and PTCL, and Orphan status from the European Medicines Agency (EMEA) for the treatment of both CTCL and PTCL. The FDA has also granted Fast Track status for CTCL and PTCL. A New Drug Application submission for romidepsin in CTCL was accepted by the FDA for review, with a PDUFA date in November of 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 histone deacetylase (HDAC) inhibitor, is in late-stage development for T-cell lymphomas and has shown activity across a range of hematologic malignancies. Gloucester has submitted a New Drug Application with the Food and Drug Administration based on the results of a registration trial of romidepsin in patients with cutaneous T-cell lymphoma (CTCL). The Company is currently 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.