Cidara Therapeutics and Melinta Therapeutics recently announced that Rezzayo (rezafungin for injection) has been approved by the US Food and Drug Administration (FDA). The antifungal drug was approved under Priority Review based on its Qualified Infection Disease Product designation, an incentive to promote development of antifungals for life-threatening infections.
Candidemia is a bloodstream infection caused by the Candida yeast and is a common form of invasive candidiasis. Candida normally lives in the body and on the skin without causing issues, but in the subset of patients who are at risk (e.g., those with central venous catheters, the immunocompromised and those who receive a lot of antibiotics), it can infect the bloodstream, organs and bones. Candidemia is the most common cause of bloodstream infections in hospitalized patients, resulting in prolonged hospital stays or death, as well as high medical costs.
The first line of treatment for invasive candidiasis is a subset of antifungal medications called echinocandins, which includes caspofungin (brand name Cancidas), the drug that rezafungin was compared with in clinical trials. Echinocandins act as a non-competitive inhibitor of β-(1, 3)-D-glucan synthase, an enzyme needed for the integrity of the fungal cell wall. Once the fungus cannot synthesize β-(1, 3)-D-glucan, it undergoes osmotic instability and cell death.
Rezzayo is a novel, next-generation echinocandin that has been approved for the treatment of candidemia and invasive candidiasis in adults over the age of 18 who have limited or no alternative treatment options.
As Rezzayo is the first new echinocandin in over ten years to be approved by the FDA, it is a milestone for both companies and patients with the deadly infection. Rezzayo can potentially simplify treatment from once-daily (with caspofungin) to once-weekly.
Christine Ann Miller, president and CEO of Melinta Therapeutics, says Melinta is “working closely with Cidara and anticipate bringing Rezzayo, a differentiated once-weekly treatment to patients, this summer.”
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Similarities Between Rezafungin and Caspofungin in Candidiasis Treatment
The efficacy of rezafungin was investigated in the ReSTORE Phase III trial, and the approval of the once-weekly injection is based upon the results of the study, which have been published in The Lancet.
The trial was a multicenter, double-blind, double-dummy, randomized Phase III trial across 66 tertiary care centers in 15 countries. Adults aged 18 years or older were randomly assigned to received intravenous rezafungin once a week (400 mg the first week, then 200 mg weekly for two to four more doses) or intravenous caspofungin (70 mg loading dose on the first day, then 50 mg daily for no more than four weeks).
The primary endpoints were global cure (consisting of clinical cure, radiological cure and mycological eradication) at 14 days for the European Medical Agency (EMA), and a 30-day all-cause mortality for the US FDA. Rezafungin met the endpoints outlined by both the EMA and FDA.
Fifty-nine percent of the patients on rezafungin and 61 percent of patients on caspofungin had global cure at day 14, and 24 percent of patients on rezafungin and 21 percent of patients on caspofungin died or had unknown survival status at day 30.
Overall, rezafungin demonstrated statistical non-inferiority compared to caspofungin, and the rates of adverse events (AEs) for both treatments were comparable (91 percent for the rezafungin group, and 85 percent for the caspofungin group), including rates of AEs leading to study discontinuation.
The Phase III results support the ongoing development of rezafungin based on efficacy and safety.
George Thompson, MD, principal investigator in the ReSTORE trial and professor of clinical medicine at the University of California, Davis, School of Medicine, stated that “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.”
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Approval of Rezzayo Contributes to Growth of Echinocandin Market
Approximately two million deaths occur annually due to fungal infections, and fungi grow resistant to antifungals over time. Antimicrobial resistance is increasingly a threat to public health, and the need for novel antifungals is critical in conjunction with actions that are being taken by groups like the US Centers for Disease Control and Prevention (CDC), and can be performed by healthcare providers and patients.
The echinocandins market is expected to grow from 515 million in 2021 to 797 million by 2029 due to a rise in fungal infections and the need to improve healthcare infrastructure. Echinocandins offer a number of advantages to other antifungal medications including fewer drug-drug interactions, unique mechanism of action and fewer AEs.
Rezafungin is currently being studied for its efficacy in preventing invasive fungal diseases caused by Candida, Aspergillus and Pneumocystis spp. in patients undergoing blood and bone marrow transplants.
Other companies are also conducting investigations into echinocandins. For example, Scynexis Inc. is currently recruiting for a Phase III trial for candidiasis treatment with echinocandins followed by a treatment arm of oral ibrexafungerp (brand name Brexafemme) or oral fluconazole (brand name Diflucan) in adults.
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