Background: Micafungin (FK463) is a new lipopeptide compound (echinocandin) with activity against Aspergillus and Candida species. This study evaluated the safety and efficacy of micafungin in patients with proven or probable invasive aspergillosis (IA). Methods: A multinational, non-comparative study was conducted to examine proven or probable (pulmonary only) Aspergillus species infection in a wide variety of patient populations. The study employed an open-label design utilizing micafungin alone or in combination with another systemic antifungal agent. Criteria for IA and therapeutic responses were judged by an independent panel. Results: Of the 331 patients enrolled, only 225 met diagnostic criteria for IA as determined by the independent panel and received at least one dose of micafungin. Patients included 98/225 who had undergone hematopoietic stem cell transplantation (HSCT) (88/98 allogeneic), 48 with graft versus host disease (GVHD), and 83/225 who had received chemotherapy for hematologic malignancy. A favorable response rate at the end of therapy was seen in 35.6% (80/225) of patients. Of those only treated with micafungin, favorable responses were seen in 6/12 (50%) of the primary and 9/22 (40.9%) of the salvage therapy group, with corresponding numbers in the combination treatment groups of 5/17 (29.4%) and 60/174 (34.5%) of the primary and salvage treatment groups, respectively. Of the 326 micafungin-treated patients, 183 (56.1%) died during therapy or in the 6-week follow-up phase; 107 (58.5%) deaths were attributable to IA. Conclusions: Micafungin as primary or salvage therapy proved efficacious and safe in high-risk patients with IA, although patient numbers are small in the micafungin-only groups.
Bibliographical noteFunding Information:
DWD, in the past 5 years, has received grant support from Astellas, Merck, Pfizer, F2G, OrthoBiotech, Indevus, Basilea, the Fungal Research Trust, the Wellcome Trust, the Moulton Trust, the National Institute of Allergy and Infectious Diseases and the European Union. He has been an advisor/consultant to Merck, Basilea, Vicuron (now Pfizer), Schering-Plough, Indevus, F2G, Nektar, Daiichi, Sigma Tau, Astellas, PPL Therapeutics and Uriach. He has been paid for talks on behalf of Astellas, Merck, GSK, Chiron, AstraZenca and Pfizer. He holds founder shares in F2G Ltd.
TFP has consulted for and received grant support from Astellas, Bristol-Myers Squibb, Merck, Pfizer, and Schering-Plough. He has received grant support from Enzon. He has consulted for Affinium, Basilea, Diversa, Eisai, J. Uriach and Cía.S.A., MediciNova, Microbia, Nektar Therapeutics, Rib-X Pharmaceuticals, and Vicuron. He is on the speakers' bureaus for Astellas, Enzon, Merck, and Pfizer Inc.
- Amphotericin B