What Is Rezzayo (Rezafungin)?
Rezafungin is the first representative of the second-generation class of echinocandins [citation]. Rezzayo (Rezafungin) is an antifungal drug for patients with limited or no alternative treatment options for candidemia and invasive candidiasis. Candida infections accounted for 40% of all invasive fungal infections. In such diagnoses, echinocandins are recommended as first-line antifungal agents. Rezafungin was approved by the FDA on March 22nd, 2023 [citation; citation].
What Are Echinocandins?
Echinocandins are antifungal drugs used to treat invasive fungal infections, particularly those caused by Candida species. They work by inhibiting the synthesis of a crucial fungal cell wall component, called beta-(1,3)-D-glucan. Echinocandins have shown efficacy against a broad range of Candida species and are considered an important treatment option in patients with severe fungal infections.
For What Is Used Rezzayo (Rezafungin)?
Rezafungin is indicated for patients diagnosed with candidemia or invasive candidiasis who are 18 or older [citation]. Candidemia and invasive candidiasis are rare, serious, and life-threatening infections. On average, 9 out of 100,000 people become infected with this infection [citations], and it is the fourth leading cause of nosocomial bloodstream infections in the United States of America (USA) and the seventh in Europe [citation]. Candida infections are related to the areas of the mouth and throat or are related to vaginal infections. Invasive candidiasis seriously affects the brain, eyes, bones, blood, heart, and the like [citation].
Patients usually have systemic signs and mycological confirmation of candidemia or invasive candidiasis. This medicine is usually given once weekly. The initial dose of Rezafungin is administered intravenously and contains 400 mg of the drug (in the first week). In the second week, the dose is reduced to 200 mg. Per the prescription, a precise dose should be given to the patient within a month [citation; citation; citation].
Rezafungin has orphan drug status, which indicates a promising outcome in treating, preventing, and diagnosing orphan diseases [citation; citation].
What Are Nosocomial Bloodstream Infections?
Nosocomial bloodstream infections, also known as hospital-acquired bloodstream infections, occur during a hospital stay or as a result of healthcare interventions. They involve the presence of bacteria, viruses, or fungi in the bloodstream, which can lead to severe complications and increased morbidity and mortality. These infections often arise from invasive medical devices, surgical procedures, or exposure to healthcare-associated pathogens in the hospital environment.
Who Developed Rezzayo (Rezafungin)?
Cidara and Melinta Therapeutics developed Rezzayo. These companies are focused on producing drugs for acute and life-threatening diseases [citation].
Cidara Therapeutics is a biopharmaceutical company that focuses on developing novel antifungal and immunotherapy treatments to address severe fungal infections and other infectious diseases. Their innovative approach involves developing of Cloudbreak® Immunotherapy, which harnesses the immune system to fight infections, and rezafungin, a novel antifungal agent with extended dosing intervals, aiming to improve patient outcomes in treating invasive fungal infections.
Melinta Therapeutics is a pharmaceutical company dedicated to discovering, developing, and commercializing novel antibiotics to combat severe bacterial infections. They focus on addressing unmet medical needs in treating challenging bacterial pathogens, including multidrug-resistant organisms. Their portfolio includes drugs such as Baxdela® and Vabomere®, which are used to treat a range of bacterial infections, including those caused by gram-negative bacteria.
What Is the Mechanism of Action?
Rezafungin belongs to the group of drugs with fungicidal activity and is an inhibitor of the 1,3-β-D-glucan synthase enzyme [citation]. This drug destroys the main component of fungi, the 1,3-β-D-glucan synthase, which is found in the cell walls of fungi, and this leads to the prevention of 1,3-β-D-glucan formation [citation]. By blocking the 1,3-β-D-glucan synthase enzyme, Rezafungin disrupts the formation of the fungal cell wall, leading to cell wall weakening, cell lysis, and, ultimately, fungal cell death. Candida spp infections are treated this way, but the effect has also been confirmed for Aspergillus spp [citation].
What Are the Key Advantages of Rezzayo (Rezafungin)?
The following items mark the main advantages of Rezafungin:
The key solution for adults with limited or no alternative treatment options for candidiasis and invasive candidemia (Adequate for isolates where resistance to other echinocandins has been confirmed);
High effectiveness for mycoses (Oesophageal candidiasis, Invasive candidemia, and the prevention of mycoses in transplant patients);
Effectiveness against: Candida spp., Aspergillus spp., Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum gypseum;
It is also prescribed to patients with immunosuppressive therapy (patients with a weakened immune system, e.g., people who have AIDS, cancer, or neutropenia);
And for the prevention of Pneumocystis spp. Pneumonia [citation].
What Are the Key Warnings and Precautions?
Clinical data and efficacy for Rezzayo approval are limited. Some of the drug warnings are related to the following:
Infusion-related reactions (Flushing, Sensation of warmth, Urticaria, Nausea, and Chest tightness)[citation],
Photosensitivity. Because of this phenomenon, patients are recommended to avoid exposure to UV rays and the sun [citation];
Hepatic Adverse Reactions [citation];
They are not prescribed to pregnant women due to embryotoxicity [citation;citation].
Due to Candida, Rezzayo has not been studied in patients with endocarditis, osteomyelitis, and meningitis [citation].
Susceptibility to echinocandins may be caused by a mutation in glucan synthase catalytic subunit-encoding FKS genes (FKS1 and/or FKS2). In addition, this drug can create cross-resistance, but resistance to Rezzayo is insufficiently described. Therefore, to successfully guide patients, it is recommended to follow the susceptibility test interpretive criteria proposed by the FDA [citation; citation].
What Are the Key Adverse Reactions?
Adverse reactions have been reported mainly in about 5% of cases so far and are mainly related to the following symptoms:
Anemia,
Abdominal pain,
Constipation,
Diarrhea,
Hypokalemia,
Hypomagnesemia,
Hypophosphatemia,
and Vomiting [citation].