New trial reaffirms safety of Genasense

High-dose intravenous infusions (IV) of so-called ‘first generation’ antisense compounds, known as phosphorothioates, have been associated with severe toxicity in monkey studies. As a consequence, clinical use of these drugs has sought to avoid high plasma concentrations by using continuous IV administration of low doses.

During its Phase III clinical trials, Genta developed a safety database involving patients who tolerated accidental overdoses, which suggested that the animal experience might not be clinically predictive.

Additional preclinical data have also suggested that intermittent high-dose injections are associated with equal or superior antitumor efficacy. The company has now developed clinical data that establishes Genasense can be safely administered by both subcutaneous injection as well as brief IV infusion.

Dr Anthony Tolcher, director of clinical research, South Texas Accelerated Research Therapeutics (START), and clinical professor of medicine, University of Texas Health Science Center, San Antonio, said: “This study is remarkable since it overturns more than a decade of preconceived safety notions based on animal toxicology that we now show was highly misleading. More patients have received Genasense than all other DNA- or RNA-based medicines combined. Our data show that new schedules of Genasense can be readily developed that do not involve indwelling catheters or protracted IV infusions.”