Pharmacokinetic evaluation of oblimersen sodium for the treatment of chronic lymphocytic leukemia

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western hemisphere. Developing new therapies remains a priority as present treatment options do not offer a cure. BCL-2 overexpression in CLL is associated with aggressive disease features and resists chemotherapy. Oblimersen sodium (G3139) is a phosphorothioate oligonucleotide antisense drug targeting the BCL-2 mRNA and is the first antisense to reach advanced clinical testing in oncology. Preclinical evaluation has demonstrated good antineoplastic effect in B-cell cancers; several clinical trials have confirmed its safety and efficacy both alone and in combination with other therapeutics.

Areas covered: This review focuses on the chemistry, pharmacodynamics, pharmacokinetics and clinical evaluation of oblimersen in CLL. PubMed and MEDLINE searches assisted in data collection.

Expert opinion: Bcl-2 is an important target in CLL. Antisense therapy is a novel approach to target oncoproteins; this can be beneficial in the clinical setting. Oblimersen sodium demonstrates the clinical safety of the antisense therapeutic approach and, with chemotherapy, shows survival advantage in a subset of CLL patients. However, future approval of oblimersen sodium in CLL remains uncertain. Nevertheless, BCL-2 remains a critical target in drug development and is an area of high-priority research.

Keywords::

• antisense oligonucleotide
• antisense oligonucleotide therapy
• Bcl-2
• chronic lymphocytic leukemia
• oblimersen sodium
• phosphorothioate oligonucleotide

Acknowledgements

The authors thank L Itri of Genta, Inc. for providing them with the molecular structure of oblimersen sodium.