Presentation of preclinical data demonstrating the combination of ISTODAX and Velcade announced

Gloucester Pharmaceuticals announced today the presentation of preclinical data demonstrating that the combination of ISTODAX® (romidepsin) and Velcade® (bortezomib) resulted in synergistic anti-tumor activity in B-cell non-Hodgkin's lymphoma cell lines. ISTODAX is a member of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors. The results were presented during a poster presentation entitled, “The Combination of Romidepsin and Bortezomib Results in Synergistic Induction of Apoptosis in Human B-Lymphoma Cell Lines” at the 51st American Society of Hematology (ASH) Annual Meeting being held in New Orleans, LA.

“The results in this in vitro combination study of ISTODAX and Velcade suggest this may be an important clinical combination to test in patients with relapsed or refractory B-cell malignancies,” said Sagar Lonial, MD, Associate Professor, Hematology and Medical Oncology at Emory University School of Medicine and an author of the study. “We are currently conducting mechanistic studies with the goal of identifying predictors of response that can be validated in prospective clinical trials and look forward to presenting these results at a future scientific meeting.”

“ISTODAX has been studied extensively in T-cell lymphomas and was recently approved by the FDA for the treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy,” said Jean Nichols, PhD, President and Chief Operating Officer of Gloucester Pharmaceuticals. “These preclinical results in B-cell lymphoma cell lines build on previous work presented in multiple myeloma and suggest that the combination of ISTODAX and Velcade may have a potential role in the broader hematologic space and merit additional study.”

Study Results:

Four B-cell lymphoma lines (Daudi, HT, Ramos and SUDHL-4) were exposed to different combinations of ISTODAX and Velcade separately, concurrently and sequentially. The combination of ISTODAX and Velcade resulted in synergistic B-cell apoptosis. Order-of-addition experiments demonstrated definite sequence specificity. When ISTODAX was administered first and followed six hours later by administration of Velcade, cell growth was arrested in the G2/M phase and cell death was increased compared to both agents being given concurrently or Velcade being administered first. Protein level expression analyses suggest that the combination affected both aggresome formation and autophagy. The observed effects of the combination of ISTODAX and Velcade on B-cell lymphoma lines at low nanomolar concentrations suggests that this may be an important clinical combination to test in patients with relapsed or refractory B-cell malignancies.



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