Alemtuzumab (Millennium/ILEX).

Alemtuzumab, a lymphocyte-depleting humanized monoclonal antibody, is being developed by Millennium Pharmaceuticals Inc and ILEX Oncology for the potential treatment of chronic lymphocytic leukemia (CLL) [274580]. The utility of the compound for treating bone marrow (BM) stem cell transplantation-associated graft-versus-host disease (GVHD) [372946] and for ex vivo purging of BM to remove malignant T-cells [244056] is also being investigated. Additional potential therapeutic areas for which clinical trials are planned or ongoing include vasculitis, multiple sclerosis [288762] and organ transplantation [338304]. A Biologics License Application (BLA) was filed with the FDA in December 1999 by ILEX and Millennium [351523], [351524], [373873]. The FDA accepted the application for filing in February 2000 [355775] and returned a complete response letter in June 2000 [372172]. Millennium and ILEX submitted a response to the FDA in August 2000 [379766]. Alemtuzumab has received Fast Track designation [304771] and orphan drug status from the FDA [288762], and the drug was reviewed by the FDA's Oncologic Drugs Advisory Committee on 14 December, 2000 [387228]. The committee voted 14 to 1 to recommend accelerated approval of alemtuzumab for patients with CLL who have been treated with alkylating agents and who have failed fludarabine therapy [393778], [393894]. In March 2000, Millennium and ILEX also submitted a Marketing Authorization Application (MAA) for alemtuzumab to the European Agency for the Evaluation of Medicinal Products (EMEA) [363595]. In October 2000, EMEA accepted the MAA for alemtuzumab under the agency's centralized approval procedure [387228]. Alemtuzumab was originally synthesized by Herman Waldmann and colleagues at Cambridge University and licensed to Burroughs Wellcome (BW) via the British Technology Group (BTG) [162622]. BW conducted phase I and II trials for a broad range of indications, but then discontinued development because of disappointing results in phase II rheumatoid arthritis trials [326848]. In April 1997, LeukoSite licensed rights to the antibody from BTG for the treatment of CLL and prolymphocytic leukemia, plus an option to develop it for other indications. BW agreed to supply LeukoSite with intellectual property [244056], [326848]. In May 1997, LeukoSite entered into a joint venture with ILEX Oncology for the further development of alemtuzumab [245986]. By the end of 1999, Millennium acquired LeukoSite with commitment to pursue development of the compound through the joint venture Millennium & ILEX Partners LP [351523], [370237]. In August 1999, Schering AG and its US affiliate Berlex Laboratories obtained exclusive worldwide marketing rights for alemtuzumab, excluding Japan and East Asia. In the US, Berlex, Millennium and ILEX will divide profits from alemtuzumab sales equally [337702], [338837].