What is the new drug for Niemann-Pick disease?

October 11, 2025 •

3 min read

For decades, there were no U.S. Food and Drug Administration (FDA)-approved treatments available to address the underlying causes of Niemann-Pick disease. This has recently changed with the approval of several new medications, fundamentally altering the therapeutic landscape for this rare genetic disorder. The question, 'What is the new drug for Niemann-Pick disease?' now has a multifaceted answer, with different treatments available for specific types of the condition.

Quick Summary

Several new drugs have been approved to treat different types of Niemann-Pick disease, a rare genetic disorder caused by lipid accumulation in cells. These include Xenpozyme (olipudase alfa) for types A/B (ASMD) and Miplyffa (arimoclomol) and Aqneursa (levacetylleucine) for type C (NPC), marking a major breakthrough in disease-specific therapy.

Key Points

FDA Approvals for NPC: In September 2024, the FDA approved two first-ever drugs for Niemann-Pick disease type C (NPC): Miplyffa (arimoclomol) and Aqneursa (levacetylleucine).
Xenpozyme for ASMD: Xenpozyme (olipudase alfa) was approved in 2022 as the first enzyme replacement therapy for Niemann-Pick disease types A and B, addressing non-central nervous system manifestations.
Aqneursa's Monotherapy: Aqneursa is approved as an oral monotherapy for the neurological symptoms of NPC and has shown significant improvement in clinical trials.
Miplyffa's Combination Approach: Miplyffa is approved for use in combination with the existing drug miglustat to treat NPC neurological symptoms.
Different Mechanisms of Action: These new drugs work in different ways, with Xenpozyme replacing a missing enzyme, Miplyffa enhancing cellular function, and Aqneursa correcting the underlying genetic pathology.
Pipeline Advancements: Research continues with other candidates in clinical trials, like Trappsol Cyclo for NPC, signaling further advancements in rare disease treatment.
Hope for Patients: The approval of these targeted therapies represents a monumental shift from previous supportive care, offering genuine hope for slowing disease progression.

Understanding Niemann-Pick Disease

Niemann-Pick disease (NPD) is a rare inherited metabolic disorder caused by a genetic mutation, preventing the body from properly transporting and storing lipids (fats). This leads to harmful lipid buildup in organs and the brain. There are three main types:

Type A/B (ASMD): Caused by a mutation in the $SMPD1$ gene, leading to a deficiency of the acid sphingomyelinase enzyme and sphingomyelin accumulation. Symptoms include enlarged liver/spleen, respiratory infections, and severe neurodegeneration in Type A.
Type C (NPC): Caused by mutations in $NPC1$ or $NPC2$ genes, affecting cholesterol and lipid transport out of lysosomes. Lipid accumulation impacts the brain, liver, spleen, and lungs, causing progressive neurological issues like ataxia, speech/swallowing difficulties, and cognitive decline.

Historically, NPD treatment focused on symptom management. However, recent advancements have introduced specific therapies targeting the disease's underlying pathology.

Xenpozyme (Olipudase Alfa) for ASMD

In August 2022, the FDA approved Xenpozyme (olipudase alfa-rpcp) for non-CNS manifestations of ASMD. This was the first disease-specific treatment for this form of NPD.

How Xenpozyme works

Xenpozyme is an enzyme replacement therapy (ERT) that replaces the deficient acid sphingomyelinase (ASM) enzyme. Administered intravenously, it helps break down accumulated sphingomyelin. Clinical trials showed sustained improvements in key disease indicators.

Therapeutic benefits and limitations

Xenpozyme has been shown to improve lung function, reduce liver and spleen size, and demonstrated sustained long-term benefits. However, it does not treat neurological symptoms as it does not cross the blood-brain barrier.

Dual Breakthroughs for Niemann-Pick Type C

September 2024 brought the simultaneous FDA approval of Miplyffa and Aqneursa for NPC, the first approved therapies for this condition.

Miplyffa (Arimoclomol)

Miplyffa activates transcription factors (TFEB, TFE3) to improve lysosomal function and lipid processing. It is approved for neurological symptoms in NPC patients aged 2+ when used with miglustat. Trials showed it slowed disease progression in combination with miglustat.

Aqneursa (Levacetylleucine)

Aqneursa is a modified amino acid drug targeting and correcting the genetic defect in NPC, reducing lipid accumulation. Approved as an oral monotherapy for neurological symptoms in adult and pediatric NPC patients weighing ≥15 kg. Phase III trials showed significant improvement in neurological signs and symptoms.

Comparison of New Niemann-Pick Medications


Feature	Xenpozyme (Olipudase alfa)	Miplyffa (Arimoclomol)	Aqneursa (Levacetylleucine)
Disease Target	ASMD (NPD types A/B)	NPC (NPD type C)	NPC (NPD type C)
Therapy Type	Enzyme Replacement Therapy	Lysosomal Function Enhancer	Modified Amino Acid Therapy
Mechanism	Replaces deficient ASM enzyme.	Upregulates lysosomal genes to improve lipid processing.	Corrects underlying genetic pathology.
Administration	Intravenous infusion every two weeks.	Oral capsules, three times daily, in combination with miglustat.	Oral capsules, up to three times daily.
Target Manifestations	Non-CNS symptoms (liver, spleen, lungs).	Neurological manifestations.	Neurological manifestations.
FDA Approval Date	August 2022.	September 20, 2024.	September 25, 2024.
Monotherapy/Combination	Monotherapy	Combination therapy (with miglustat).	Monotherapy.

The Future of Niemann-Pick Disease Treatment

The approval of Xenpozyme, Miplyffa, and Aqneursa has revolutionized NPD treatment. Other candidates like Trappsol Cyclo and Azafaros are also in development. These advancements represent a significant step towards precision medicine, offering hope for patients.

Conclusion

Recent FDA approvals mark a major turning point in Niemann-Pick disease treatment. Xenpozyme treats ASMD systemic issues, while Miplyffa and Aqneursa target NPC neurological decline. This shift provides hope for better management and improved quality of life for patients.

Frequently Asked Questions

The new drug for Niemann-Pick disease types A/B (also known as Acid Sphingomyelinase Deficiency, or ASMD) is Xenpozyme (olipudase alfa), which was approved by the FDA in August 2022.

Yes, two new drugs for Niemann-Pick disease type C (NPC) were approved by the FDA in September 2024: Miplyffa (arimoclomol) and Aqneursa (levacetylleucine).

Xenpozyme is an enzyme replacement therapy that replaces the deficient acid sphingomyelinase (ASM) enzyme, helping to break down the lipid buildup in cells and improving non-central nervous system symptoms.

Miplyffa works by enhancing the function of lysosomes, the cellular compartments responsible for processing lipids. It is used in combination with miglustat to slow the progression of neurological symptoms.

Aqneursa is an oral monotherapy that acts as a modified amino acid, addressing the underlying genetic pathology of NPC and improving neurological symptoms, such as ataxia.

Common side effects of Miplyffa include upper respiratory tract infections, diarrhea, and decreased weight.

No, Xenpozyme (olipudase alfa) is not expected to cross the blood-brain barrier and therefore does not address the neurological symptoms associated with the most severe form of ASMD (Type A).

Yes, other therapies are in the pipeline, including Trappsol Cyclo (a cyclodextrin formulation) for NPC, which is currently in Phase III clinical trials.