Government and Regulations

FDA panel backs antifungal for invasive aspergillosis, mucormycosis

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Novel agents hold promise

Dr. Daniel Ouellette, FCCP, comments: Serious fungal infections are being increasingly recognized in patients who are immunocompromised or critically ill, but effective treatments with an acceptable side-effect profile have been sparse. Just a few years ago, the mainstay of treatment was amphotericin, an agent whose use has been associated with a variety of complications. However, novel agents have been developed that hold promise. The recent development of isavuconazonium, a pro-drug of isavuconazole, may lead to further augmentation of the clinician's armamentarium in fighting these illnesses.


 

AT AN FDA ADVISORY COMMITTEE MEETING

References

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

emechcatie@frontlinemedcom.com

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