Collaboration to Meet a Therapeutic Need: The Development of Nelarabine

The development of nelarabine as a therapeutic agent to treat various forms of hematologic malignancies spans more than 40 years. From the bench top to the bedside, basic scientists and clinical scientists in the pharmaceutical industry and academia collaborated with regulatory agencies to bring this drug to the market. Studies have demonstrated efficacy in treating T-cell leukemia and lymphoma and further work is ongoing as new dosing schedules of nelarabine and combinations with other chemotherapeutic agents are explored. This work is aimed at maximizing the therapeutic outcome while minimizing the potential neurotoxicity that has been identified with nelarabine. This brief review provides some of the “milestones” of development and presents a summary of the efforts of the pharmaceutical industry, academia, and government. Nelarabine, synthesized in the late 1970’s as a prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is still undergoing rigorous clinical evaluations in an effort to identify its optimal use.