FDA Approves Isavuconazonium Sulfate for Pediatric Fungal Infections

Invasive aspergillosis and invasive mucormycosis are common adverse effects (AEs) that are predominantly seen in patients who are immunocompromised, such as patients with leukemia.

The FDA has approved isavuconazonium sulfate (Cresemba), an anzole antifungal, for the treatment of invasive aspergillosis or invasive mucormycosis in pediatric patients who are 1 year and older, according to a press release from Astellas Pharma US, Inc.¹

Invasive aspergillosis and invasive mucormycosis are common adverse effects (AEs) that are predominantly seen in patients who are immunocompromised, such as patients with leukemia.

The approval is based on the data from a phase 2, open-label, non-comparative, multicenter study (NCT03816176), which assessed the safety, tolerability, and efficacy of isavuconazonium sulfate in pediatric participants.

“The recent COVID-19 pandemic drove an uptick in these serious and life-threatening fungal infections, presenting an even greater urgency to address this growing unmet medical need,” Lynn Fenicchia, senior vice president and Head of US Medical Specialties Business Unit at Astellas, said in the press release.1 "Patients are waiting, and we know that young [patients with invasive aspergillosis or invasive mucormycosis] are most at risk. Today's approval will bring hope to this highly vulnerable patient population with limited treatment options."

A total of 31 pediatric patients received 10 mg/kg of isavuconazonium sulfate orally or intravenously every 8 hours for 48 hours, followed by a daily maintenance dose of 10 mg for up to 84 days for those with invasive aspergillosis and 180 days for those with invasive mucormycosis. Oral isavuconazonium sulfate was only eligible for patients between 6 to 17 years of age and who weighed at least 16 kg.

The primary end points for this trial included the number of patients with treatment-emergent AEs, and all-cause mortality through day 42. Secondary end points included overall responses, clinical responses, radiological responses, mycological responses, and pharmacokinetics.

Inclusion criteria included patients who had proven, probable, or possible invasive fungal infection as per the European Organization for Research and Treatment of Cancer/Mycoses Study Group 2008 criteria, patients with sufficient Galactomannan (GM) levels, and patients with adequate venous access to allow for intravenous administration of the drug or the ability to swallow oral capsules. Those who used prior prophylactic antifungal therapy were eligible for the study as well.

Patients were excluded from participating if they had familial short QT syndrome, evidence of hepatic dysfunction, had used strong cytochrome P450 (CYP3A4) inhibitors or inducers 5 days prior to the first dosing, had another fungal infection excluding invasive aspergillosis or invasive mucormycosis, had chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis, had history of allergy, hypersensitivity or any serious reaction to any of the azole class antifungals, or had a life expectancy of less than 30 days.

Isavuconazonium sulfate has been approved for treating patients 18 years and older with invasive aspergillosis or invasive mucormycosis since receiving FDA approval in March 2015.²

This approval was based on the phase 3 SECURE trial (NCT00412893), a randomized, double-blind, active-control study of adult patients with invasive aspergillosis, and the phase 3 VITAL trial (NCT01731353), an open-label non-comparative study of isavuconazonium sulfate in adult patients with invasive aspergillosis and renal impairment or in patients with invasive fungal disease caused by other rare fungi.^3,4

References:

1. FDA approves expanded use of CRESEMBA® (isavuconazonium sulfate) in children with invasive aspergillosis and invasive mucormycosis. Astellas Pharma US, Inc. News release. December 8, 2023. Accessed December 8, 2023. https://tinyurl.com/yjjkhedj
2. Astellas receives FDA approval for CRESEMBA® (isavuconazonium sulfate) for the treatment of invasive aspergillosis and invasive mucormycosis. News release. March 6, 2015. Accessed November 28, 2023. prn.to/3QtPpOO
3. Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760-769. doi:10.1016/s0140-6736(15)01159-9
4. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828-837. doi:10.1016/s1473-3099(16)00071-2