FDA extends adrabetadex NDA review for infantile-onset Niemann-Pick disease type C

Beren Therapeutics said the FDA has extended the review period for the new drug application (NDA) for adrabetadex in infantile-onset Niemann-Pick disease type C (I-NPC), moving the Prescription Drug User Fee Act target action date to November 17, 2026.¹ The investigational therapy is an intrathecal 2-hydroxypropyl-β-cyclodextrin formulation being reviewed for a pediatric neurodegenerative disorder with rapid progression and limited disease-modifying options.

“We are committed to working with the Agency, physicians, and NPC families to deliver this critical therapy for patients living with infantile-onset NPC as quickly as possible,” Jason Camm, CEO of Beren Therapeutics, said in the company announcement.¹

According to Beren, the 3-month extension followed the company’s March 18, 2026, response to an FDA information request that included updates and clarifications to existing data and supporting documentation. The FDA classified the response as a major amendment to the NDA, which extends the review clock by 3 months under agency procedures.¹ The agency has not announced an approval decision, and adrabetadex remains unapproved by the FDA or any other health authority, according to the company.

Adrabetadex previously received FDA priority review. The product has also received orphan drug designation and breakthrough therapy designation, regulatory pathways intended to support the development or review of therapies for serious or rare diseases when statutory criteria are met.¹ Beren stated that eligible patients may continue to receive adrabetadex through an ongoing expanded access program while the review is pending.

NPC is a rare autosomal recessive lysosomal lipid trafficking disorder most often caused by pathogenic variants in NPC1 and, less commonly, NPC2. Defective intracellular cholesterol trafficking leads to accumulation of unesterified cholesterol and other lipids, with systemic and neurologic manifestations that vary by age at onset.² I-NPC generally refers to patients whose neurologic symptoms begin before age 6 years. Earlier neurologic onset is associated with faster progression and poorer survival; Beren cited mean ages of death of approximately 5.6 years for early infantile onset and 13.4 years for late-infantile onset.¹

The clinical need in I-NPC remains substantial. Care typically requires multidisciplinary management of dysphagia, seizures, movement disorders, developmental regression, pulmonary complications, nutrition, and hearing or vision issues. In the United States, the FDA approved arimoclomol in combination with miglustat in 2024 for neurologic manifestations of NPC in adults and pediatric patients aged 2 years and older, marking an important regulatory milestone but not eliminating the need for additional therapies across age groups and disease stages.³

Adrabetadex is described by Beren as a proprietary mixture of 2-hydroxypropyl-β-cyclodextrin isomers suitable for intrathecal administration. The therapeutic rationale is based on targeting impaired cholesterol trafficking in NPC. Prior clinical experience with intrathecal 2-hydroxypropyl-β-cyclodextrin in NPC has suggested potential slowing of neurologic progression compared with historical controls, although interpretation has been constrained by small sample sizes, open-label designs, disease heterogeneity, and reliance on natural history comparisons.⁴

Safety monitoring will be central if the product advances. Beren reported that the most common adverse events observed with adrabetadex have included hearing impairment, postdose fatigue, and ataxia.¹ Hearing loss has also been a recognized concern in prior intrathecal cyclodextrin development in NPC, underscoring the likely importance of baseline and longitudinal audiologic assessment in clinical use or continued access programs.⁴

The current FDA action is best interpreted as a procedural update rather than a determination of efficacy, safety, or approvability. The company announcement did not include new efficacy analyses, updated trial outcomes, or detailed subgroup data specific to the NDA review. Key unanswered issues include the final indicated population, dosing schedule, intrathecal administration requirements, monitoring recommendations, and how benefits and risks may differ across the broad infantile-onset spectrum.

For clinicians caring for children with NPC, the extended review means that regulatory clarity is now expected in November 2026, while expanded access remains the only route described by the company for eligible patients to receive adrabetadex outside of a potential approval.

References

1. Beren Therapeutics. Beren Therapeutics announces FDA extension of review period for New Drug Application (NDA) for adrabetadex for the treatment of infantile-onset Niemann-Pick disease, type C. Business Wire. Published May 28, 2026. https://www.businesswire.com/news/home/20260528306754/en/Beren-Therapeutics-Announces-FDA-Extension-of-Review-Period-for-New-Drug-Application-NDA-for-Adrabetadex-for-the-Treatment-of-Infantile-Onset-Niemann-Pick-Disease-Type-C

2. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5:16. Published 2010 Jun 3. doi:10.1186/1750-1172-5-16

3. US Food and Drug Administration. FDA approves first treatment for Niemann-Pick disease, type C. Published September 20, 2024. Accessed May 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c

4. Ory DS, Ottinger EA, Farhat NY, et al. Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial. Lancet. 2017;390(10104):1758-1768. doi:10.1016/S0140-6736(17)31465-4