Gloucester Pharmaceuticals Announces Positive Results from Romidepsin T-cell Lymphoma Clinical Trials at ASH

–Exceeds primary endpoint in CTCL registration trial and confirms high response rates and sustained duration of response previously reported; NDA submission anticipated by year-end–

–Demonstrates positive single-agent activity in Phase 2 PTCL trial; Supportive of ongoing PTCL registration study–

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 8, 2008 - Gloucester Pharmaceuticals today announced positive results from the Company's registration trial in cutaneous T-cell lymphoma (CTCL) and from a Phase 2 trial in CTCL and peripheral T-cell lymphoma (PTCL) conducted by the National Cancer Institute (NCI) 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 hematologic malignancies. Additionally, positive data emerging from a clinical trial of romidepsin in combination with Velcade® (bortezomib) and dexamethasone in multiple myeloma will be presented later at the meeting.

In an oral presentation entitled Clinically Significant Responses Achieved with Romidepsin in Treatment-Refractory Cutaneous T-Cell Lymphoma (CTCL): Final Results from a Phase 2B, International, Multicenter, Registration Study, Dr. Youn H. Kim of the Stanford Cancer Center described the results. In the study, evaluable patients refractory to prior therapy who received romidepsin had an overall response rate of 42% (30/72) [95% confidence interval (CI): 30, 54]. This exceeded the primary endpoint of the study which required the lower bound of the 95% CI be above 15%. Responses were observed at all stages of disease, including an overall response rate of 48% (23/48) in patients with Stage IIB or greater disease and an overall response rate of 43% (6/14) in patients with Stage IVA disease. Importantly, despite the exclusion of steroid and antihistamine use, most (63%) patients with moderate to severe pruritus at baseline experienced significant pruritus relief, a key indicator of clinical benefit.

Data from a supportive study in CTCL were also presented in a poster entitled Final Clinical Results of a Phase 2 NCI Multicenter Study of Romidepsin in Recurrent Cutaneous T-Cell Lymphoma (CTCL) by Dr. Susan Bates of the NCI. This study is sponsored by the NCI under a Cooperative Research and Development Agreement (CRADA) with Gloucester. Final results from the Phase 2 NCI study in CTCL are consistent with the results demonstrated in the CTCL registration study and further support the Company's pending New Drug Application (NDA) submission. The overall response rate in evaluable patients was 40% (25/63). Responses were observed at all stages of disease, including an overall response rate of 36% (20/55) in patients with Stage IIB or greater disease and an overall response rate of 29% (10/34) in patients with Stage IVA/B disease.

Complete results from both studies follow in a table below.

CTCL Clinical Program Final Results
    Registration Study - GPI-04-0001   Supportive Study - NCI 1312*
  Evaluable** n=72   As-Treated n=96   Evaluable** n=63   As-Treated n=71
Overall Response Rate, n (%)   30 (42%)   33 (34%)   25 (40%)   25 (35%)
Complete Response, n (%)   6 (8%)   6 (6%)   4 (6%)   4 (6%)
Partial Response, n (%)   24 (33%)   27 (28%)   21 (33%)   21 (30%)
Median Duration of Response   Not reached   14.9 months   11.0 months   11.0 months
Median Time to Progression   17.7 months   8.3 months   6.6 months   6.5 months
*Skin involvement measured with Physician's Global Assessment.
**Evaluable patients received at least 2 cycles of romidepsin.

“The data from the registration study are consistent with previously reported positive results from the NCI study,” said Dr. Kim. “Importantly, romidepsin was well-tolerated and demonstrated marked activity across all stages of disease. Romidepsin also demonstrated high response rates in patients with Stage IIB or greater disease, including patients with Sézary syndrome. If approved, romidepsin may offer substantial hope and fill a significant treatment void for patients with CTCL.”

“We continue to be very pleased with the results of the CTCL development program,” said Dr. Jean Nichols, President and Chief Operating Officer of Gloucester Pharmaceuticals. “Of particular interest, the median duration of response across all 167 patients in the CTCL program exceeds one year. This finding is noteworthy given the brevity of responses typically seen with other agents used to treat CTCL. Additionally, most of the adverse events associated with romidepsin in the registration study were mild in nature and supportive of the drug candidate's substantial safety profile with more than 750 patients having received romidepsin in clinical trials to date.”

Data from the NCI study in PTCL, also sponsored by the NCI under the CRADA, were also presented today in a poster entitled Results of a Phase 2 NCI Multicenter Study of Romidepsin in Patients with Relapsed Peripheral T-Cell Lymphoma (PTCL) by Dr. Richard Piekarz of the NCI. The overall response rate in evaluable patients was 44% (15/34) and the median duration of response was nine months. Of note, the Company believes that the sustained duration of response seen in this study may meet a significant unmet medical need in this relapsed, refractory patient population. Earlier data from this study provided the rationale for the Company's ongoing registration study in PTCL which is currently enrolling patients. The Phase 2 NCI data continue to mature and the Company anticipates that updated results will be presented a future scientific meeting. There are currently no FDA-approved therapies for PTCL.

Complete results from this study follow in a table below.

Phase 2 PTCL Interim Results
    NCI 1312
  Evaluable* n=34   As-Treated n=48
Overall Response Rate, n (%)   15 (44%)   15 (31%)
Complete Response, n (%)   4 (12%)   4 (8%)
Partial Response, n (%)   11 (32%)   11 (23%)
Median Duration of Response   9.0 months   9.0 months
Median Time to Progression   Not available   12.0 months
*Evaluable patients received at least 2 cycles of romidepsin.

“The comprehensive data package presented at ASH supports romidepsin's growing profile as an exciting new drug candidate with potential broad utility across a number of hematologic malignancies,” said Dr. Alan Colowick, Chief Executive Officer of Gloucester Pharmaceuticals and a specialty-trained hematologist. “While romidepsin has demonstrated significant single-agent activity, the positive results to be presented later at this meeting in combination with Velcade® in multiple myeloma also point to the potential role romidepsin could play as a combination agent in improving the standard of care for other difficult to treat hematologic diseases. Pending the submission and approval of the NDA for CTCL and continued positive data in PTCL and multiple myeloma, we believe romidepsin could be a welcome addition to the treatment armamentarium.”

About the Phase 2B Registration Study of Romidepsin in Treatment-Refractory CTCL

This study is a single-arm, open-label trial of romidepsin in patients with treatment-refractory CTCL conducted at 33 sites in eight countries. The study enrolled 96 patients who received 14 mg/m2 of romidepsin infused on days 1, 8 and 15 every 28 days.

Overall, the most common drug-related adverse events (AEs) in this study were mild (Grade 1-2) and included gastrointestinal symptoms (68%), asthenic conditions (44%), hematological toxicities (26%) and anorexia (20%). The only study drug-related serious AE reported in more than one patient was tumor lysis syndrome (2%). Romidepsin did not have a significant effect on the QT interval. In an ECG analysis, a modest increase in mean QTcF of 4.6 milliseconds (msec) was observed following infusion of romidepsin.

About the Phase 2 Romidepsin NCI CTCL/PTCL Trial

NCI Study 1312 is a Phase 2, open-label trial of romidepsin in patients with CTCL and PTCL conducted at the NCI and nine additional sites in the United States and Australia. The study enrolled 71 patients with CTCL and 48 patients with PTCL. Patients received 14 mg/m2 of romidepsin infused on days 1, 8 and 15 every 28 days.

Overall the AE profile in this study for patients with CTCL was consistent with that previously reported. The most frequent drug-related AEs were generally mild, including gastrointestinal symptoms (85%), fatigue (73%), electrocardiogram T-wave amplitude decrease (69%) and hematologic toxicities (59%). Drug-related serious AEs included hyperuricemia (6%), hypotension, infection NOS, supraventricular arrhythmia NOS, ventricular arrhythmia NOS, neutropenia, leukopenia (4% each), anorexia, aspartate transaminase increased, catheter-related infection, dehydration, dyspepsia, injection site reaction NOS, nausea and thrombocytopenia (3% each).

Overall the adverse event profile in the study for patients with PTCL was consistent with that previously reported. The most frequent drug-related AEs were generally mild, including gastrointestinal symptoms (67%), hematologic effects (65%), electrocardiogram T-wave amplitude decrease (65%), fatigue (63%) and anorexia (40%). The most frequent Grade 3 or higher drug-related adverse events were hematologic toxicities (42%), fatigue (13%) and gastrointestinal symptoms (8%).

Romidepsin did not have a significant effect on the QT interval in assessed patients with either CTCL or PTCL. In an ECG analysis, a modest increase in mean QTcF of 4.5 msec was observed following infusion of romidepsin.

Upcoming Presentations

Additional romidepsin results will be presented this evening, Monday, December 8, from 5:30 to 7:30 PM Pacific Time 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 I/II Clinical Trial” presented by Simon J. Harrison of the Peter MacCallum Cancer Centre, Melbourne during the “Myeloma – Therapy, excluding Transplantation Session.”

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.

 

 

Contact: MacDougall Biomedical Communications
Sarah Cavanaugh, 781-235-3060

 

Posted: December 2008

View comments

Hide
(web5)