Poster: Early evidence of an emerging NPC treatment paradigm: adrabetadex use alongside arimoclomol and/or N‑acetyl‑L‑leucine

Citation: Berry-Kravis E, et al. Early evidence of an emerging NPC treatment paradigm: adrabetadex use alongside arimoclomol and/or levacetylleucine. Poster presented at: National Niemann-Pick Disease Foundation (NNPDF) Family and Medical Conference; July 2026.

Plain Language Summary: Until recently, families living with NPC had very few treatment options. Today, several therapies that work in different ways are becoming available. This study is the first to describe how these therapies are being used together in clinical practice and what that may mean for the future care of patients with NPC.

What is this study about?

This analysis looked at how an investigational treatment called adrabetadex has been used together with two other recently approved NPC treatments, arimoclomol and levacetylleucine (NALL). 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. Infantile-onset NPC (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 of NPC.

Until recently, there were very few approved treatments for NPC. Now, with multiple treatments available that work in different ways, researchers want to understand how to use these treatments together in the best way possible. This is the first study to look at how and when patients received these treatments in combination as part of an expanded access program (EAP), which is a program that allows patients with serious conditions to access investigational treatments outside a clinical trial.

What are these treatments, and how do they work?

The four treatments studied each work differently:

• Adrabetadex: investigational treatment that helps restore the normal movement of cholesterol inside cells, addressing the underlying biological problem that causes NPC. Adrabetadex is investigational, meaning it is still being studied and has not been approved by the U.S. Food and Drug Administration (FDA).
• Levacetylleucine / NALL: may improve how nerve cells produce energy. It is FDA-approved for patients with NPC who weigh at least 15 kg/33 lbs.
• Arimoclomol: helps cells respond to stress, although the exact mechanism is unknown. It is FDA-approved for use in combination with miglustat in patients with NPC aged 2 years and older.
• Miglustat: reduces the production of certain lipids that build up in NPC cells. It is not FDA-approved for NPC but is approved in other countries and is often used alongside the above therapies.

Who participated, and what did the study do?

The study reviewed data from an adrabetadex EAP, which began in 2013 and included patients with NPC who were not eligible or able to enroll in clinical trials. Patients in the EAP were allowed to continue or add other approved NPC therapies as they became available, including arimoclomol and NALL after they received FDA approval.

Of the 85 patients enrolled in the EAP, 33 had received adrabetadex together with arimoclomol and/or NALL as of March 1, 2026. The study described the characteristics of these patients, when and in what order they received each treatment, and what combination patterns were identified.

What the study found:

• Most physicians chose to keep patients on adrabetadex after newer therapies became available, adding the newer medicines rather than replacing adrabetadex. 
• 33 patients had received adrabetadex alongside arimoclomol and/or NALL. Of these: 

• 6 received adrabetadex + arimoclomol;
• 12 received adrabetadex + NALL; 
• 15 received all three (adrabetadex + arimoclomol + NALL), 10 of which were exposed to all four therapies (+ miglustat)

• Most patients (28 of 33) started adrabetadex first and then added arimoclomol and/or NALL after those treatments received FDA approval. For most patients, adrabetadex remained the foundation of treatment as newer therapies became available.
• A smaller group (5 patients) had started arimoclomol before adrabetadex treatment. These patients received arimoclomol for an average of about 3.7 years before adding adrabetadex.
• More than half of the 33 patients had I-NPC, defined by neurological symptoms beginning before age 6. I-NPC is the most severe and fastest-progressing form of the disease, and more than 30% had early infantile-onset, with symptoms appearing before age 2, a group with the most limited treatment options.
• 32 of the 33 patients remained active in the adrabetadex EAP at the time of this analysis.
• Because each treatment works differently, doctors hope they may complement one another by addressing different aspects of NPC. Researchers are continuing to study whether combination treatment leads to better outcomes than using any single therapy alone.

Why does this matter?

NPC is a complex disease that causes ongoing damage over time, even with treatment. Because available treatments work in different ways, clinicians have considered whether using them together could offer greater benefit than any single treatment alone. A recent expert consensus statement noted that combination treatment should be considered for most NPC patients but acknowledged that there is limited real-world data to guide decisions.

For the first time, physicians have experience combining multiple NPC therapies. These findings suggest that combination treatment is practical and that many clinicians are choosing to build on adrabetadex rather than replace it when new therapies become available. 

What this means for patients:

These findings suggest that adrabetadex may become the foundation of treatment for many patients with NPC, with additional therapies added over time based on individual needs. This represents an important step toward a future where multiple therapies are used together to help patients living with this serious disease.

This is meaningful first evidence that a multi-treatment approach to NPC treatment is emerging in practice and may be laying the groundwork for a new standard of care for patients with this serious disease.

What this means for families:

Until recently, families living with NPC had very few treatment options. As new therapies become available, doctors are beginning to use multiple treatments together rather than relying on a single treatment alone.

This analysis shows that many patients who started adrabetadex continued receiving it after newer treatments became available, with additional treatments added based on their individual needs. This suggests that, rather than replacing one another, treatments that work in different ways may increasingly be used together as part of a personalized approach to care.

While more research is needed to understand the benefits of combination treatment, these findings provide early evidence that a new approach to treating NPC is emerging. For families, this means there may be more opportunities for doctors to tailor treatment over time, with the goal of helping patients receive the greatest possible benefit from available treatments.