Gloucester Pharmaceuticals Announces Positive Results from Phase 1/2 Multiple Myeloma Clinical Trial at ASH–High response rates demonstrated in combination study of romidepsin®– December 9, 2008 Cambridge, MA Gloucester Pharmaceuticals yesterday announced positive interim results from a Phase 1/2 combination study of romidepsin, Velcade® (bortezomib) and dexamethasone in patients with relapsed or refractory multiple myeloma at the 50th American Society of Hematology (ASH) Annual Meeting in San Francisco, CA. Romidepsin is a novel, cyclic peptide, histone deacetylase inhibitor under investigation for the treatment of hematologic malignancies. Additional positive data from a single-agent registration study in cutaneous T-cell lymphoma (CTCL) and from a Phase 2 study in CTCL and peripheral T-cell lymphoma (PTCL) were also presented earlier this week in oral and poster presentations respectively. A New Drug Application submission for romidepsin in CTCL is expected by year-end and a registration study in PTCL is currently recruiting patients. In a poster presentation entitled High Response Rates with the Combination of Bortezomib, Dexamethasone and the Pan-Histone Deacetylase Inhibitor Romidepsin in Patients with Relapsed or Refractory Multiple Myeloma in a Phase 1/2 Clinical Trial, Dr. Simon J. Harrison of the Peter MacCallum Cancer Centre in Melbourne, Australia described the results to date. In the study, patients with relapsed or refractory multiple myeloma who received romidepsin in combination with Velcade® and dexamethasone had an overall response rate of 85% (17/20). Four (20%) patients achieved a complete response (CR), two (10%) a very good partial response, six (30%) a partial response (PR) and five (25%) a minor response (MR). Five of six patients previously exposed to Velcade® responded in this study, including a negative immunofixation CR, one PR and three MRs. The median time to progression for all patients was seven months. "While romidepsin has demonstrated significant single-agent activity in other difficult to treat cancers, the high response rates observed in this combination study in a relapsed or refractory patient population are very exciting," said Dr. Harrison. "The combination of romidepsin and Velcade® also demonstrated activity in patients who had previously failed Velcade® treatment suggesting that, with further study, romidepsin could improve the standard of care for patients with multiple myeloma. I continue to be very enthusiastic about romidepsin and the role this important drug candidate may be able to play in treating a number of hematologic diseases." "The positive data Gloucester presented in CTCL, PTCL and now multiple myeloma at ASH strongly support the potential broad utility of our novel histone deacetylase inhibitor, romidepsin, as both a single-agent and in combination therapy," said Dr. Alan Colowick, Chief Executive Officer of Gloucester Pharmaceuticals. "We continue to make significant strides in the development of romidepsin and expect to submit a New Drug Application for romidepsin for the treatment of CTCL by the end of year." About the Phase 1/2 Romidepsin Multiple Myeloma Trial The Phase 1/2 study is an open-label, single-center, single-arm, dose-escalating trial of romidepsin in combination with Velcade® and dexamethasone followed by maintenance romidepsin therapy until disease progression. In the Phase 1 portion of the study which enrolled 10 patients, the maximum tolerated dose was determined to be 10 mg/m2 of romidepsin, 1.3 mg/m2 of Velcade® and 20 mg of dexamethasone. To date, this ongoing study has enrolled 22 patients, with 20 patients currently evaluable for response. Patients receive romidepsin on days 1, 8 and 15, receive Velcade® on days 1, 4, 8 and 11 and receive dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12. The most common adverse events were sensory or motor neuropathy (41%), nausea (36%), fatigue (32%), constipation/diarrhea (32%), infection (32%) and cyclic thrombocytopenia (27%). The most common Grade 3/4 adverse events were sensory or motor neuropathy (18%), infection (14%) and cyclic thrombocytopenia (14%). This study continues to enroll patients and the Company anticipates that updated results will be presented at a future scientific meeting. 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 recently 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 durable 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 750 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 is anticipated in late 2008. 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 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 late 2008. 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. Velcade® is a registered trademark of Millennium: The Takeda Oncology Company. |