Antisense Therapeutics: A Promise Waiting to Be Fulfilled

During the past decade, only one antisense-based therapy has received full Food and Drug Administration (FDA) approval. Vitravene™, developed by Isis Pharmaceuticals, was the first drug based on antisense technology to be successfully commercialized and used in treatment (1 ). The therapeutic area it is used in is a small niche related to the treatment of preventing blindness in acquired immunodeficiency syndrome (AIDS) patients by inhibiting cytome-galovirus-induced retinitis. The success of Vitravene, however, showed that antisense could be taken all the way through the FDA approval process and provide those patients taking it with a vitally important effect. With Vitravene we saw the first breakthrough in antisense therapy, and, yet, euphoria has turned to disappointment without a second breakthrough. Subsequent trials of Affinitak (Isis), an antisense inhibitor of protein kinase C α, failed to show statistically significant benefits as an antisense therapy for the treatment of non-small cell carcinoma of the lung better than the median survival with control treatments. The results nevertheless proved that antisense was well tolerated and tended toward greater benefit to the survival of patients (p <0.054). The promise of antisense therapy is so attractive that some 20 trials continue.