Eraxis (anidulafungin)

Eraxis (anidulafungin) is an echinocandin semi-synthetic lipopetide, designed to eradicate fungal infections through disruption of enzyme synthesis pathways in these cells without affecting human tissues.

Eraxis is specifically indicated for the treatment of several types of fungal infections: Candidemia; intra-abdominal abscess and peritonitis caused by Candida species; and esophageal candidiasis. The drug has not been studied for the treatment of Candida related endocarditis, osteomyelitis, or meningitis, and efficacy in the treatment of neutropenic patients has not been fully established.

Eraxis is supplied as a lyophilized powder for reconstitution and injection. The recommended initial dose of the drug for the treatment of Candidemia/additional Candida infections is a single loading dose of 200 mg Eraxis on day 1, followed by 100 mg daily thereafter, until clinical response is observed (generally through at least 14 days after the last positive fungal culture). For esophageal candidiasis, recommended dosing is a single loading dose of 100 mg on day 1, followed by 50 mg daily thereafter for at least 14 days and at least 7 days following the resolution of symptoms.

FDA Approval
Candidemia/Additional Candida Infections
Approval of Eraxis for the treatment of Candidemia and additional Candida infections was based on a phase III trial. This randomized, double-blind, controlled study treated 256 patients with candidemia and/or other forms of invasive candidiasis. Subjects received a fixed dose regimen of either Eraxis (200 mg loading dose/100 mg daily maintenance dose) or fluconazole (800 mg loading dose/400 mg daily maintenance dose) via intravenous infusion for 14 to 42 days. Patients from either arm were permitted to transfer to oral fluconazole following at least 10 days of IV therapy and a negative blood culture. At the end of IV treatment, treatment 75.6% of subjects receiving Eraxis achieved global clinical success, vs. 60.2% for fluconazole. Superiority was maintained at the end of all treatment, (74.0% global success, vs. 56.8%, respectively), and at 2-week (64.6% vs. 49.2%) and 6-week (55.9% vs. 44.1%) follow-ups. All-cause mortality during the study (22.8% vs. 31.4%) all cause mortality during study therapy (7.9% vs. 14.4%), and mortality attributed to Candida (1.6% vs. 4.2%) all showed reductions for Eraxis relative to fluconazole.

Esophageal Candidiasis
Approval of Eraxis for the treatment of esophageal candidiasis was based on a double-blind, double-dummy, randomized phase III trial. 601 subjects were randomized to receive Eraxis (100 mg loading dose/50 mg daily maintenance dose) or fluconazole (200 mg loading dose/100 mg daily maintenance dose) via intravenous infusion. Treatment was administered for a minimum of 14 days, and for 7 days following the resolution of symptoms, through a maximum of 21 days. In both treatment groups, median time to resolution of symptoms was 5 days, and median duration of therapy was 14 days. Endoscopic success (the combined rate of clinical improvement and cure) at the end of therapy (the trial's primary endpoint) was 97.4% for Eraxis and 98.7% for fluconazole; this included cure rates of 88.3% vs. 93.6%, respectively, and improvement rates of 9.1% vs. 5.1%. At 2-weeks post-treatment subjects receiving Eraxis experienced significantly more endoscopically-documented relapses (53.3%) than subjects receiving fluconazole (19.3%).

Ongoing Study Commitments

• Deferred pediatric study under PREA for the treatment of candidemia and other forms of Candida infections (intra-abdominal abscess and peritonitis) in pediatric patients ages zero months to sixteen years of age.
  Final Report Submission: February 17, 2011

Adverse events associated with the use of Eraxis may include, but are not limited to, the following:

• Diarrhea
• Hypokalemia
• Liver Enzyme Abmormalities
• Headache
• Rash
• Neutropenia
• Nausea

Anidulafungin is a semi-synthetic echinocandin designed to inhibit glucan synthase, an enzyme present in fungal (but not mammalian) cells. Inhibition of glucan synthase disrupts formation of 1,3-ß-D-glucan, an essential component of the fungal cell wall.

Turner MS, Drew RH, Perfect JR Emerging echinocandins for treatment of invasive fungal infections. Expert Opinion on Emerging Drugs 2006 May;11(2):231-50

Benjamin DK Jr, Driscoll T, Seibel NL, Gonzalez CE, Roden MM, Kilaru R, Clark K, Dowell JA, Schranz J, Walsh TJ Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections. Antimicrobial Agents and Chemotherapy 2006 Feb;50(2):632-8

Karlowsky JA, Hoban DJ, Zhanel GG, Goldstein BP In vitro interactions of anidulafungin with azole antifungals, amphotericin B and 5-fluorocytosine against Candida species. International Journal of Antimicrobial Agents 2006 Feb;27(2):174-7. Epub 2006 Jan 18

Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ, Goldstein BP Effectiveness of anidulafungin in eradicating Candida species in invasive candidiasis. Antimicrobial Agents and Chemotherapy 2005 Nov;49(11):4795-7

For additional information regarding Eraxis or Candida fungal infections, please visit the Eraxis web page.