FDA Accepts sNDA for Isavuconazonium Sulfate in Pediatric Fungal Infections

The FDA has accepted a supplemental new drug application for the antifungal agent isavuconazonium sulfate (Cresemba) as a treatment for patients 17 years or younger with invasive mucormycosis or invasive aspergillosis, fungal infections that may occur in immunocompromised patients such as those with leukemia, according to a press release from Astellas.¹

Supporting data for the sNDA came from a phase 2 study (NCT03816176) assessing the efficacy, safety, and pharmacokinetics of isavuconazonium sulfate in pediatric patients with invasive aspergillosis or invasive mucormycosis. Investigators will present detailed findings from their study at an upcoming medical meeting.

The FDA has set a Prescription Drug User Fee Act date of December 9, 2023 for isavuconazonium sulfate in this indication.

“While rare in the general population, invasive aspergillosis or invasive mucormycosis can be incredibly dangerous for immunocompromised children, including those faced with blood and other cancers, and there are very limited treatment options,” Tadaaki Taniguchi, MD, PhD, chief medical officer at Astellas, said in the press release. “The collective efforts by our research and development teams, which have led to the successful sNDA acceptance for [isavuconazonium sulfate] by the FDA, reflect our ongoing commitment to addressing vulnerable populations with high unmet medical needs.”

Isavuconazonium sulfate, a prodrug the of anzole antifungal drug isavuconazole, is currently indicated for treating patients 18 years and older with invasive aspergillosis or invasive mucormycosis after receiving FDA approval in March 2015.²

In the open-label, non-comparative, multi-center phase 2 trial, pediatric patients will receive a loading dose of isavuconazonium sulfate intravenously or orally every 8 hours on days 1 and 2 followed by maintenance dosing once a day. Treatment will continue for up 84 days in those with invasive aspergillosis and up to 180 days in those with invasive mucormycosis.

The study’s primary end points include adverse effects, vital sign abnormalities, laboratory value abnormalities, and all-cause mortality. Secondary end points include overall responses, clinical responses, radiological responses, mycological responses, and pharmacokinetics.

Patients 1 to 17 years old with a proven, probable, or possible invasive fungal infection per European Organisation for Research and Treatment of Cancer/Mycoses Study Group 2008 criteria and adequate Galactomannan levels were eligible for enrollment on the study. Additional eligibility criteria included having sufficient venous access for intravenous administration of the study treatment.

Those with evidence of hepatic dysfunction or prior use of strong cytochrome P450 inhibitors within 5 days of beginning study treatment were not eligible for enrollment. Patients were also unable to enroll on the study if they had another invasive fungal infection other than invasive aspergillosis or invasive mucormycosis, chronic aspergillosis, or received mould active systemic antifungal therapy. Having an allergy or hypersensitivity to azole class fungal drugs or a life expectancy lower than 30 days were also grounds for exclusion from the trial.

“Since its approval over 8 years ago, [isavuconazonium sulfate] has been helping adult patients and their physicians fight certain life-threatening fungal infections when they are often critically ill with other diseases. This sNDA acceptance by the FDA brings Astellas one step closer to helping pediatric patients by potentially having a new treatment option available for [invasive aspergillosis] and [invasive mucormycosis] for a younger patient population, if approved,” Lynn Fenicchia, senior vice president and head of U.S. Medical Specialties Business Unit at Astellas, concluded.

References

1. U.S. FDA accepts Astellas’ sNDA for CRESEMBA® (isavuconazonium sulfate) in children. News release. Astellas. August 10, 2023. Accessed August 11, 2023. bit.ly/3DWJjPe
2. Astellas receives FDA approval for CRESEMBA® (isavuconazonium sulfate) for the treatment of invasive aspergillosis and invasive mucormycosis. News release. March 6, 2015. Accessed August 11, 2023. prn.to/3QtPpOO