Anidulafungin effective against ARMC

April 1, 2005

Washington — Anidulafungin (Vicuron, Vicuron Pharmaceuticals Inc.), a new echinocandin presently being developed for the treatment of serious fungal infections, has been shown to be effective and well-tolerated in a large majority of patients who have azole-refractory mucosal candidiasis (ARMC), said Jennifer A. Schranz, M.D., in a presentation at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy here.

Washington - Anidulafungin (Vicuron, Vicuron Pharmaceuticals Inc.), a new echinocandin presently being developed for the treatment of serious fungal infections, has been shown to be effective and well-tolerated in a large majority of patients who have azole-refractory mucosal candidiasis (ARMC), said Jennifer A. Schranz, M.D., in a presentation at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy here.

Most azole-refractory mucosal candidiasis patients in the study had advanced AIDS with low CD4 cell counts, says Dr. Schranz, director of clinical research, Vicuron Pharmaceuticals.

"Anidulafungin's efficacy in the treatment of these patients is important because, while the incidence of oroesophageal candidiasis (OPC) and esophageal candidiasis (EC) has decreased with the advent of highly active antiretroviral therapy (HAART), OPC and EC are still significant problems for those who are failing or are non-adherent to HAART."

Occurrence Oroesophageal and esophageal candidiasis occur, not only in patients who are immunosuppressed as a result of advanced HIV infection, but also in patients who are immunosuppressed due to malignancies, post-transplantation immunosuppressive therapy, persistent neutropenia, steroid use, diabetes or autoimmune disease, she says.

Up to now, the optimal treatment for ARMC has been unknown. An effective and well-tolerated antifungal agent could greatly benefit patient management.

With this in mind, Dr. Schranz says, a noncomparative, open-label, multicenter study was conducted in the United States from August 2002 to August 2004 to assess the efficacy of intravenous (IV) anidulafungin as a treatment for 19 patients with ARMC. Seventeen patients had AIDS, and the remaining two patients had documented connective tissue diseases (rheumatoid arthritis and Sjogren's syndrome). Anidulafungin was given IV at a loading dose of 100 mg on day one, followed by 50 mg IV on day two through 14 (minimum) to 21 (maximum) in these patients with ARMC, defined as OPC or EC that failed to resolve following a prior 14-day course of fluconazole of at least 200 mg daily or voriconazole (Vfend, Pfizer) at any dose. Clinical response at the end of treatment (EOT) was successful, measured as cure or improvement or failure. Successful endoscopic response was cure, described as endoscopic grade 0, or improvement, described as a reduction of at least one grade; failure was no change or worsening of endoscopic grade. Also, safety was assessed and adverse events collected.

"As noted earlier, anidulafungin was highly effective in the treatment of ARMC," Dr. Schranz says. "A total of 17 of 18 patients or 94 percent with oropharyngeal candidiasis were clinical successes at end of treatment, and 92 percent (11/12) of patients with esophageal candidiasis were both clinical and endoscopic successes at EOT. The antifungal agent was well-tolerated, and only one adverse event, characterized as a rash, led to discontinuation of the study drug."

Sustained responses Clinical responses were sustained at follow-up for approximately half of the EC patients, Dr. Schranz tells Dermatology Times. Not surprisingly, in this group of patients with persistent immunosuppression unresponsive to treatment, relapse occurred in approximately half of the patients. Patients with ARMC will probably require ongoing antifungal maintenance therapy after induction therapy with anidulafungin to prevent relapse until immune reconstitution is achieved. In this population with few treatment options, these data suggest that anidulafungin is a useful alternative therapy, Dr. Schranz concludes.

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