New Drug Application Submitted for Investigational Therapy for Infantile-Onset Niemann-Pick Disease Type C

A New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for adrabetadex (Mandos, Thousand Oaks, CA), an investigational therapy for the treatment of infantile-onset Niemann-Pick disease type C (NPC). The application seeks approval based on evidence of improved survival reported in those taking adrabetadex compared with external controls, supported by biomarker and nonclinical data intended to demonstrate effects on the underlying disease pathology. Priority Review was requested, and the FDA has a 60-day period to determine whether the NDA will be accepted for review.

Adrabetadex is a cyclodextrin therapy designed to enhance intracellular cholesterol trafficking, a central defect in NPC. The NDA submission is intended to serve as a single adequate and well-controlled study using an externally controlled survival analysis in patients with infantile-onset NPC along with confirmatory biomarker evidence and patient experience data.

According to a statement from Beren Therapeutics, the parent company of Mandos, data highlighted in the NDA submission include the following:

• Survival analyses showed improved outcomes in adrabetadex-treated patients with infantile-onset NPC compared with matched external control populations.
• Biomarker analyses demonstrated reductions in markers of neuronal injury, including fatty acid–binding protein 3 and calbindin D.
• Treatment was associated with increases in 24S-hydroxycholesterol, a biomarker of neuronal cholesterol trafficking, supporting a mechanistic rationale for the observed survival findings.
• Adrabetadex was generally well tolerated, with the most commonly reported adverse events including hearing impairment, transient fatigue, and post-dose ataxia.

Adrabetadex received Breakthrough Therapy Designation in 2025 for infantile-onset NPC. The sponsor plans to continue providing access to the therapy through an Expanded Access Program during the FDA review process.