Alexander Gold, MD, on Adrabetadex’s Impact in Infantile-Onset Niemann-Pick C

Infantile-onset Niemann-Pick disease type C (NPC) is a devastating, ultra-rare neurodegenerative disorder in which impaired intracellular cholesterol trafficking leads to toxic accumulation within neurons. Patients who develop neurological symptoms before age 6 typically experience rapid functional decline and shortened survival, underscoring the critical need for disease-modifying therapies.

At the 2025 Child Neurology Society (CNS) Annual Meeting, held October 8-11 in Charlotte, North Carolina, investigators shared new survival and biomarker data on adrabetadex, an investigational intrathecal therapy developed by Mandos Health by Beren Therapeutics P.B.C. The results, led by Elizabeth Berry-Kravis, MD, PhD, demonstrated a statistically significant survival benefit in children with infantile-onset NPC compared with matched external controls, along with biomarker findings supporting restoration of cholesterol trafficking and reduced neuronal injury.

In this conversation with NeurologyLive, Alexander Gold, MD, chief medical officer of Mandos Health, discussed the mechanism of adrabetadex, the survival analysis presented at CNS 2025, and the broader collaborative progress being made across the NPC community.

NeurologyLive: For our clinical audience, what is the mechanism and rationale behind adrabetadex for treating patients with infantile-onset NPC?

Alexander Gold, MD: Adrabetadex* is a proprietary mixture of 2-hydroxypropyl-β-cyclodextrin isomers under investigation by Mandos Health by Beren Therapeutics P.B.C. as a potential treatment for NPC. NPC is a rare, progressive, neurodegenerative disorder characterized by impaired cholesterol trafficking that leads to toxic accumulation of cholesterol within cells, especially neurons. Patients with NPC with neurological symptom onset between the ages of 0-6 (“infantile-onset”) are the most severe cases, with a worse prognosis that can lead to premature death.

By re-establishing intracellular neuronal cholesterol trafficking, adrabetadex directly addresses the core pathology of NPC, In our clinical studies, treatment with adrabetadex has been associated with increased cerebrospinal fluid levels of 24(S)-hydroxycholesterol, which are typically low in individuals with NPC, reflecting restoration of cholesterol trafficking within neurons. At the same time, adrabetadex decreased levels of calbindin D and fatty acid-binding protein 3 (FABP3), biomarkers associated with neuronal injury and death. These data support the biological rationale for adrabetadex and reinforce our belief in its disease-modifying potential for individuals with NPC.

For those who couldn’t attend CNS, could you share some key insights and takeaways from the survival analysis you presented? What stood out most clinically?

At the Child Neurology Society meeting, we presented a survival analysis of participants with infantile-onset NPC – those with neurological symptom onset before six years of age – who received intrathecal adrabetadex in clinical trials and an ongoing Expanded Access Program (sponsored by Mandos Health). Survival in the treated group was compared to matched, untreated external controls derived from four major natural-history sources.

These analyses incorporate long-term treatment data and rigorous methodology, enabling a deeper understanding of how adrabetadex may impact survival and disease progression in this population.

One of the key takeaways is how the results reinforce the therapeutic potential of addressing the underlying impairment of cholesterol trafficking in NPC and contribute new evidence for clinicians managing this ultra-rare condition. Overall, participants treated with adrabetadex experienced a statistically significant and clinically meaningful increase in survival compared with matched controls, demonstrating a clinically meaningful survival benefit. Taken together, the survival and biomarker findings offer a consistent picture of biological and clinical benefit for families affected by infantile-onset NPC.

What have been the main challenges in developing effective treatments for infantile-onset NPC? To that point, where have we seen the greatest improvements and collaboration within the community in recent years?

Developing effective treatments for infantile-onset NPC has been challenging due to the rarity of the disease, variability in clinical presentation, and limitations of traditional study designs. Small patient numbers, short study durations, and endpoints that lacked sensitivity to detect change have historically made it difficult to evaluate clinical efficacy. NPC affects multiple organ systems, with the most severe and debilitating effects occurring in the brain, making evaluating disease progression especially complex.

Over the past several years, Mandos Health and our collaborators in academia, advocacy, and regulatory communities have made important strides. Expanded Access Programs and shared natural history data have improved understanding of disease progression and enabled more robust analyses such as the one presented at CNS. We’ve also seen progress in the use of biomarkers that objectively connect biological activity with potential clinical outcomes. These collective efforts reflect a community-wide commitment to accelerating the development of meaningful treatment options for individuals and families affected by NPC.

When speaking with patients and families, what priorities matter most to them, and how can the clinical community continue to meet those needs?

For families affected by infantile-onset NPC, time is precious. This disease progresses rapidly, and parents often face an urgent need for therapies that can slow decline and preserve quality of life. Data showing survival benefit in adrabetadex-treated participants are meaningful because they point to the potential for more time for developmental milestones and for families to be together.

Many children with NPC still experience diagnostic delays, which can limit therapeutic opportunities. Clinicians play a vital role in recognizing early neurological symptoms, initiating appropriate biomarker and genetic testing, and referring patients to centers experienced with NPC care. As a company dedicated to this community since 2021, Mandos Health remains committed to partnering with physicians, researchers, and families to support education, access, and compassionate care through our Expanded Access Program.

*Adrabetadex is an investigational treatment and at the time of the Child Neurology Society meeting has not been approved by the U.S. Food and Drug Administration (FDA) or any other health authority at this time.

Transcript was edited for clarity. Click here for more CNS 2025 coverage.

REFERENCE
1. Data Analyses Show Benefit for Individuals With Infantile-Onset Niemann-Pick Disease Type C Treated With Investigational Drug Adrabetadex. News release. October 9, 2025. Accessed October 27, 2025. https://www.businesswire.com/news/home/20251009444024/en/Data-Analyses-Show-Benefit-for-Individuals-With-Infantile-Onset-Niemann-Pick-Disease-Type-C-Treated-With-Investigational-Drug-Adrabetadex