Efungumab: a novel agent in the treatment of invasive candidiasis.
OBJECTIVE
To review the use of efungumab as an adjunctive agent in the treatment of invasive candidiasis (IC) and to provide guidance on formulary placement.


METHODS
Searches of MEDLINE (1966-June 2009) and EMBASE (1974-June 2009) were conducted using the terms efungumab, Mycograb, heat shock protein 90, and invasive candidiasis. Other resources included www.clinicaltrials.gov and article bibliographies.


METHODS
All studies and case reports evaluating efungumab use in IC were included. Literature review was limited to the English language.


RESULTS
Efungumab is a monoclonal antibody targeted against heat shock protein 90 (HSP 90). It binds to HSP 90, preventing a conformational change needed for fungal viability. In vitro data show that HSP 90 inhibition may decrease resistance against antifungal agents and increase antifungal activity. Efungumab shows activity against Candida spp. when used alone and synergism when combined with fluconazole, caspofungin, and amphotericin B. A randomized controlled trial evaluated combination therapy of efungumab 1 mg/kg twice daily and liposomal amphotericin B versus amphotericin B therapy alone. At day 10, a favorable response was seen in 84% of patients in the efungumab group compared with 48% of patients in the placebo group (OR 5.76; 95% CI 2.4 to 13.8). Mortality at day 33 was also lower in the efungumab group, 4% versus 18%, respectively (OR 0.168; 95% CI 0.036 to 0.797). Although adverse effects were similar in this trial (10% vs 7%), case reports revealed an increased incidence of blood pressure fluctuations. Cytokine release syndrome has also been linked to efungumab use, warranting further exploration of its safety.


CONCLUSIONS
Efungumab is a new antifungal agent with a novel mechanism of action. Available clinical data and synergy studies support the use of efungumab in combination with other antifungal agents for the treatment of IC. Further safety data are needed before formulary recommendations can be made.
Auburn University Harrison School of Pharmacy, University of South Alabama, Health Services Building, Ste. 2100, Mobile, AL 36688. rzk0004@auburn.edu
Rakhi
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Karwa
Kurt A
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Wargo
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods; D005260:Female; D018841:HSP90 Heat-Shock Proteins; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000935:Antifungal Agents; D018841:HSP90 Heat-Shock Proteins; C512268:efungumab