Preclinical

Genasense^® (oblimersen sodium) Injection has been studied preclinically  in combination with many types of anticancer therapies, including chemotherapy, radiation, monoclonal antibodies and immunotherapy. Multiple preclinical studies have shown that Genasense synergizes with multiple anticancer therapies.  These studies have been conducted in experiments involving a large number of cancer types. This broad level of activity has engendered considerable scientific interest and a search by many companies and researchers for various different attacks on the Bcl-2 protein.  Genasense is the most advanced drug in the class of Bcl-2 targeted therapies.

Studies are currently underway to examine the safety and efficacy of Genasense in a variety of clinical indications.  The safety and efficacy of Genasense have not been established for any use.

• Combinations
• Temodar^® & Abraxane^®
• Nexavar^® & Abraxane^®
• Taxol^® & Sutent^®
• Intermittent Short IV Dosing

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  Preclinical Publications

  1. Kim R, et al.:  Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells.  Cancer 103:2199-207, 2005.
      
     
     
  2. Hu Y, et al.:  Antitumor efficacy of oblimersen Bcl-2 antisense oligonucleotide alone and in combination with vinorelbine in xenograft models of human non-small cell lung cancer.  Clin Cancer Res 10:7662-70, 2004.
      
     
     
  3. Klasa RJ, et al.:  Oblimersen Bcl-2 antisense:  facilitating apoptosis in anticancer treatment.  Antisense Nucleic Acid Drug Dev 12:193-213, 2002.
      
     
     
  4. Lopes de Menezes DE, Mayer LD:  Pharmacokinetics of Bcl-2 antisense oligonucleotide (G3139) combined with doxorubicin in SCID mice bearing human breast cancer solid tumor xenografts.  Cancer Chemother Pharmacol 49:57-68, 2002.
      
     
     
  5. Mu Z, Hachem P, Pollack A:  Antisense Bcl-2 sensitizes prostate cancer cells to radiation.  Prostate 65: 331 – 40, 2005.
      
     
     
  6. van de Donk NW, et al.:  Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein.  Leukemia 17:211-9, 2003.

• Intermittent Short IV Dosing Schedules

  Early clinical studies with Genasense employed continuous intravenous (IV) infusions given over a period of several days.  We are now evaluating high-dose intermittent treatment with Genasense.  Preclinically, this method has been associated with increased intratumoral drug uptake in certain animal studies.  In these experiments, intermittent (twice per week) treatment with Genasense increased the activity of paclitaxel and temozolomide, as well as multiple tyrosine kinase inhibitors, including erlotinib, imatinib, sunitinib and sorafenib, used either alone or in combination with a taxane. Genta has completed Phase 1 clinical trials evaluating intermittent dosing by both subcutaneous injection and short IV infusions over 1-2 hours. The Company has moved its twice-weekly x 3 weeks short IV infusion schedule into an ongoing Phase 2 study in melanoma.