Poster: Outcomes in participants with infantile-onset Niemann-Pick disease type C receiving prompt and sustained treatment with adrabetadex

Citation: Berry-Kravis E, et al. Outcomes in participants with infantile-onset Niemann-Pick disease type C receiving prompt and sustained treatment with adrabetadex. Poster presented at: National Niemann-Pick Disease Foundation (NNPDF) Family and Medical Conference; July 2026.

Plain Language Summary: Results of an analysis comparing disease progression in children with infantile-onset Niemann-Pick Disease Type C (I-NPC) who started adrabetadex (formerly VTS-270, cyclodextrin) within one year of their first neurological symptoms compared to those who started treatment later. This is important because damage from NPC builds up over time, and every month matters. 

What is this study about?

Children with I-NPC lose important abilities over time as the disease progresses. This study asked a simple but important question: does starting adrabetadex earlier help slow that progression over the long term? In NPC, cells cannot move cholesterol properly. As cholesterol builds up inside cells, it damages the brain and other organs, causing children to gradually lose important abilities such as walking, speaking, and swallowing. Every child's experience is different, but the disease always gets worse over time. I-NPC, where neurological symptoms begin before age 6, progresses much more rapidly and leads to more severe decline and shorter survival than later-onset forms.

How does adrabetadex work?

Adrabetadex is an investigational treatment given by lumbar puncture (injection into the spinal fluid, also known as an intrathecal injection). Adrabetadex helps restore the normal movement of cholesterol inside cells, addressing the underlying biological problem that causes NPC. It is the only investigational treatment specifically studied and shown to improve survival in both the early and late infantile-onset forms of NPC. Adrabetadex is investigational, meaning it is still being studied and has not been approved by the U.S. Food and Drug Administration (FDA).

Currently approved NPC treatments for neurological symptoms, arimoclomol and levacetylleucine, are only approved for patients who are at least 2 years old or weigh at least 15 kg (33 lbs). This leaves very young children with early I-NPC with extremely limited treatment options, making access to adrabetadex through an expanded access program (EAP) especially important for this population.

Who participated, and what did this study do?

This study identified 25 children with I-NPC from an adrabetadex EAP, which allows patients with serious conditions to receive investigational treatments outside of a formal clinical trial. To be included in this analysis, children had to meet two criteria: a diagnosis of I-NPC and at least 5 years of continuous adrabetadex treatment (some were treated for over 11 years).

The children were divided into two groups based on how quickly they started treatment after their first neurological symptoms appeared:

• Prompt treatment group (9 children): started adrabetadex within 1 year of symptom onset, on average about 7 months after symptoms began. These children started treatment at a younger age (about 1.9 years old) and had lower disease severity scores when they started treatment.
• Delayed treatment group (16 children): started adrabetadex 1 year or more after symptom onset, on average about 4.5 years after symptoms began. These children were older when treatment started (about 6.5 years old) and had higher disease severity scores when they started treatment.

Disease progression was measured using a 20-point scale called the R4DNPCCSS that rates four key everyday abilities: walking, coordinating hand movements, speech, and swallowing. Higher scores mean more difficulty with these tasks.

The key question was: does starting treatment promptly, within the first year of neurological symptoms, slow down disease progression more than if starting treatment later, and does that benefit hold up over many years of treatment?

What the study found:

• Children in the prompt treatment group who started adrabetadex within one year of their first neurological symptoms experienced slower disease progression over time than children in the delayed treatment group who started later.
• Both prompt and delayed treatment groups showed slower disease progression compared to what would be expected based on published natural history data for untreated children with NPC, where an average worsening of about 1.5 points per year has been reported. This suggests adrabetadex provides meaningful benefit regardless of when treatment begins.
• Children in the prompt treatment group began treatment with less disease burden (meaning they had lower disease progression scores at the start of treatment), which is consistent with diagnosis before the disease had accumulated more neurological damage.
• These differences suggest that starting adrabetadex earlier, targeting cholesterol buildup before significant irreversible brain damage has occurred, may offer greater long-term benefit.

Why does this matter?

NPC is progressive, so once neurological damage occurs, it cannot be reversed. This is why the timing of treatment is likely important: adrabetadex works by re-establishing cholesterol movement in cells, but if treatment starts early enough, it may be able to prevent the damage that would otherwise accumulate.

These findings add to a growing body of evidence that early diagnosis and early treatment of I-NPC are critical. They also underscore the urgent need for newborn screening programs and improved diagnostic pathways that can identify children with NPC before their disease progresses significantly.

What this means for patients:

This study suggests that children with I-NPC who begin adrabetadex soon after their first neurological symptoms may lose abilities more slowly than children who begin treatment later. While children benefited from treatment regardless of when they started, these findings reinforce the importance of diagnosing NPC early and beginning treatment as soon as possible.

What this means for families:

This analysis suggests that children with I-NPC who begin adrabetadex soon after their first neurological symptoms may experience slower disease progression over time than children who start adrabetadex treatment later. While children appeared to benefit from treatment regardless of when they started, these findings suggest that earlier treatment may provide an additional long-term advantage.

Earlier diagnosis gives families more time to understand the disease, consider treatment options, and begin therapy before more neurological abilities are lost. Together, these findings reinforce the importance of recognizing NPC early and starting adrabetadex treatment as soon as possible for appropriate children.