ICAAC 2014: New Drug Isavuconazole Is Effective Against Opportunistic Fungal Infections

A new antifungal drug, isavuconazole, matched the efficacy of voriconazole for treatment of invasive fungal infections in cancer patients with compromised immunity, but with fewer side effects, researchers reported at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy last week in Washington, DC.Isavuconazole was shown to be effective against various fungal infections that act as opportunistic illnesses in people with HIV/AIDS, including Aspergillus, Candida, and Cryptococcus.

Isavuconazole is a triazole antifungal being developed by Astellas and Basilea Pharmaceutica International, available in oral and intravenous formulations; it is under evaluation for U.S. Food and Drug Administration approval.

Andrew Ullman of Julius Maximilians University in Wuerzburg, Germany and Kieren Marr of Johns Hopkins University presented findings from the SECURE trial, comparing isavuconazole vs voriconazole for patients with and without active malignancies. All cause-mortality was similar, at approximately 25%, for uncontrolled cancer patients in both treatment groups. Drug-related adverse events, however, were less frequent in the isavuconazole group (approximately 40% vs 60%, respectively).

A related study found that isavuconazole plus amphotericin B or micafungin had synergistic activity against Candida albicans and some related species, offering the prospect of combination therapy. Another study showed that isavuconazole was effective against cryptococcal meningitis in a mouse model, which was confirmed in a small human trial.

Below is an edited excerpt from a press release from the American Society for Microbiology, which puts on conference, describing some of the research presented at ICAAC in more detail.

New Drug Against Invasive Mold Disease as Effective as Existing Drugs with Fewer Adverse Events

Washington, DC -- September 7, 2014 -- A newly developed antifungal, isavuconazole, is as effective as an existing drug, voriconazole, against  invasive mold disease in cancer patients with less adverse effects, according to Phase 3 clinical data presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, an infectious disease meeting of the American Society for Microbiology.

"There is a growing need for new antifungal therapies like isavuconazole because serious fungal infections caused by Aspergillus and other molds are on the rise due to the increasing numbers of immunosuppressed patients, including those with active cancer. These infections are associated with high morbidity and mortality. If approved, isavuconazole has the potential to be an important new option for the treatment of these life-threatening fungal infections," says Andrew Ullman of Julius Maximilians University in Wuerzburg, Germany, one of the researchers presenting data. 

Invasive fungal infections are important causes of morbidity and death for patients with hematological malignancies. Many leukemia and lymphoma patients receive high-dose chemotherapy, sometimes followed by stem cell transplantation, compromising their immune systems. The genus Aspergillus comprises several hundred species of mold that are ubiquitous in the environment but pose little threat to people with healthy immune systems. Immunocompromised patients, however, are more vulnerable to infection.

Ullman presented results from a large randomized Phase 3 study comparing the efficacy and safety of isavuconazole, a newly developed antifungal, with voriconazole in a subset of patients with uncontrolled cancer. The results showed that isavuconazole was as effective as voriconazole for treatment of invasive mold disease. In addition, isavuconazole had significantly fewer drug-related adverse events than voriconazole.

"In this study, isavuconazole had significantly fewer adverse events than voriconazole, particularly in the eye, skin, and hepatobiliary (liver, gall bladder, and bile duct) organ classes. These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease," says Kieren Marr of Johns Hopkins University who also presented data from the clinical trial.

Isavuconazole is an investigational once-daily intravenous and oral broad-spectrum antifungal being developed by Astellas and Basilea Pharmaceutica International Ltd. for the treatment of life-threatening invasive fungal infections. Recently Astellas submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for isavuconazole for the treatment of invasive aspergillosis and invasive mucormycosis (also known as zygomycosis).

This research was presented as part of the ASM’s 54th ICAAC held September 5-9, 2014 in Washington, DC.  A full press kit for the meeting, including tipsheets and additional press releases, can be found online at http://bit.ly/54icaacpk. 

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

9/12/14

References

AJ Ullman, S Shoham, W Huang, et al. A Phase 3 Randomized, Double-Blind, Non-Inferiority Trial Evaluating Isavuconazole (ISA) vs. Voriconazole (VRC) for the Primary Treatment of Invasive Fungal Disease (IFD) Caused by Aspergillus spp. or other Filamentous Fungi (SECURE): Outcomes by Malignancy Status. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-1756.

K Marr, E Bow, W Heinz, et al. A Phase 3 Randomized, Double-Blind, Non-Inferiority Trial Evaluating Isavuconazole (ISA) Vs. Voriconazole (VRC) for the Primary Treatment of Invasive Mold Infection (SECURE): Outcomes in Subset of Patients with Hematologic Malignancies (HM). 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-1757.

D Andes, M Ghannoum, L Kovanda, et al. Outcomes by Minimum Inhibitory Concentrations from Isavuconazole Phase 3 Trial of Invasive Aspergillosis (SECURE). 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-1761.

LK Najvar, NP Wiederhold, R Bocanegra, et al. Isavuconazole is Effective for the Treatment of Experimental Cryptococcal Meningitis. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-427.

V Petraitis, M McCarthy, J Meletiadis, et al. In Vitro Combination Therapy with Isavuconazole against Candida spp. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-1106.

F Queiroz-Telles, OA Cornely, J Perfect, et al. Successful Outcomes in Patients with Invasive Fungal Disease due to C. gattii and C. neoformans Treated with Isavuconazole: Experience from the VITAL Trial. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC 2014), September 5-9, in Washington, DC. Abstract M-1773.

Other Source

American Society for Microbiology. New Drug Against Invasive Mold Disease as Effective as Existing Drugs with Fewer Adverse Events. Press release. September 7, 2014.