FDA Approves Long-Acting Antifungal for Treating Candida

The FDA gave the greenlight to the long-acting antifungal rezafungin (Rezzayo), the first new treatment option for candidemia and invasive candidiasis to gain approval in over a decade, Cidara Therapeutics and Melinta Therapeutics announced on Wednesday.

Rezafungin is a weekly injectable echinocandin indicated for adults with limited or no alternative options to treat candidemia and invasive candidiasis. Rezafungin is to be administered as a 400-mg loading dose, followed by 200 mg doses weekly. The drug has not been studied for use beyond 4 weeks.

"The FDA approval of Rezzayo is tremendous news for those of us who have been hoping for a new option to treat our patients with these deadly fungal infections," said George Thompson, MD, of the University of California Davis and principal investigator of the pivotal ReSTORE trial, in the statement from the drugmakers.

"Based on the totality of clinical data generated, Rezzayo has the potential to simplify the management of invasive candidiasis and enhance the continuity of echinocandin care," Thompson added.

The drug approval follows the recommendation of an FDA advisory panel that voted 14-1 in late January in favor of a "limited use" indication. Committee members expressed concerns that the drug was not tested in the patients who would ultimately use the treatment; however, they ultimately agreed the benefits outweighed the risks.

Primary support for approval came from the phase III ReSTORE trial, which found non-inferiority on all-cause mortality at 30 days with weekly-injected rezafungin versus daily-injected caspofungin (21.3% vs 23.7%; a 2.4% difference, 95% CI -9.7 to 14.4). The phase II STRIVE clinical trial data also supported the approval.

Adverse reactions reported in at least 5% of patients include hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia.

Rezafungin has not been studied in patients with endocarditis, osteomyelitis, or meningitis due to Candida. It is contraindicated for patients with known hypersensitivity to the drug or other echinocandins -- one of four classes of antifungals (along with azoles, amphotericin B, and flucytosine) shown to have clinical effectiveness against candidemia or invasive candidiasis.

The Infectious Diseases Society of America recommends echinocandins as first-line therapy, except when infections affect the central nervous system, the eyes, or the urinary tract. Antifungals other than echinocandins are considered alternatives in the case of drug intolerance, drug-resistant pathogens, or as adjunctive therapy for refractory cases.

On its prescription labeling, rezafungin carries warnings and precautions that include infusion-related reactions (flushing, sensation of warmth, urticaria, nausea, or chest tightness). If these occur, treatment should be slowed or paused. Patients need to be warned about photosensitivity and to protect themselves from sun exposure and other sources of UV radiation while receiving rezafungin.

In addition, abnormalities in liver tests were seen in clinical trials. Patients should be monitored for abnormal liver tests, and the risks and benefits should be weighed for continuing therapy when these occur.

Rezafungin is expected to be available to patients by summer 2023.

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