Niemann-Pick Disease Type C (Overview) Management and Treatment

Niemann-Pick disease type C (NPC) is challenging to diagnose due to its heterogeneous symptoms of varying severity^1,2

Diagnosis of NPC is often delayed and misdiagnosis is common in pediatric and adult patients^1,2

NPC is a rare genetic disorder occurring in approximately 1 in 100,000 live births²
Misdiagnosis and delayed diagnosis contribute to extensive burdens on patients with NPC and their families¹:
- Physical, psychological, and intellectual impairments
- Inadequate or inappropriate management of symptoms

Signs and symptoms of NPC include neurological and cognitive impairment. These can lead to a decline in basic functions, such as gait and speech.²

Early diagnosis and proactive management of NPC can meaningfully benefit patients and their families¹

Patients with NPC urgently need treatment that provides neurological and functional improvements^1-3

According to patients and their caregivers and families, treatment for NPC should address the debilitating effects of neurological and functional decline on patients’ everyday lives.^1-3

According to a survey of 83 caregivers, families, and patients with NPC, “fewer neurological symptoms” was rated as the most meaningful treatment benefit by both patients and caregivers/families.^3,*

In the same survey, “ambulation/walking difficulties” was rated as the symptom that has the greatest impact on daily life by both patients and caregivers/families.^3,*

Patients with NPC and their families would greatly benefit from a treatment option that improves neurological symptoms and provides functional benefits that are meaningful to their everyday lives^1-3

*A meeting (in-person and via webcast) of more than 50 families was held on March 18, 2019, in Hyattsville, Maryland. The meeting was organized under the sponsorship of the FDA’s externally led Patient-Focused Drug Development (PFDD) initiative and spearheaded by the Ara Parseghian Medical Research Fund to systematically obtain the patient perspective on NPC and its treatment. Prior to the meeting, 83 individuals in the US completed a survey about their experiences with NPC and its management. Respondents to the survey included individuals with NPC, as well as both current and former caregivers.³

Discover AQNEURSA

References: 1. Geberhiwot T, Moro A, Dardis A, et al; International Niemann-Pick Disease Registry (INPDR). Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018;13(1):50. doi:10.1186/s13023-018-0785-7 2. Burton BK, Ellis AG, Orr B, et al. Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States. Mol Genet Metab. 2021;134:182-187. doi:10.1016/j.ymgme.2021.06.011 3. Kassen S, Parseghian C, Andrews P, et al. Niemann-Pick Type C Patient and Caregiver Voices: Externally-led, Patient-focused Drug Development Meeting. The Ara Parseghian Medical Research Fund at Notre Dame; 2019.

IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity

Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. The decision to continue or discontinue AQNEURSA treatment during pregnancy should consider the female’s need for AQNEURSA, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease.

Pregnancy and Lactation

For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA. Advise females of reproductive potential to use effective contraception during treatment with AQNEURSA and for 7 days after the last dose if AQNEURSA is discontinued.
There are no data on the presence of levacetylleucine or its metabolites in either human or animal milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AQNEURSA and any potential adverse effects on the breastfed infant from levacetylleucine or from the underlying maternal condition.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and greater than placebo) are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.

Drug Interactions

Avoid concomitant use of AQNEURSA with N-acetyl-DL-leucine or N-acetyl-D-leucine. The D-enantiomer, N-acetyl-D-leucine, competes with levacetylleucine for monocarboxylate transporter uptake, which may reduce the levacetylleucine efficacy.
Monitor more frequently for P-gp substrate related adverse reactions when used concomitantly with AQNEURSA; AQNEURSA inhibits P-gp; however, the clinical significance of this finding has not been fully characterized.

To report SUSPECTED ADVERSE REACTIONS, contact IntraBio Inc. at 1-833-306-9677 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

INDICATION

AQNEURSA^™ (levacetylleucine) is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg.

Please click here for Full Prescribing Information for AQNEURSA.

References: 1. AQNEURSA. Prescribing information. IntraBio. 2. Bremova-Ertl T, Ramaswami U, Brands M, et al. Trial of N-acetyl-L-leucine in Niemann-Pick disease type C. N Engl J Med. 2024;390(5):421-431. doi:10.1056/NEJMoa2310151 3. MIPLYFFA. Prescribing information. Zevra Therapeutics Inc; 2024. 4. Geberhiwot T, Moro A, Dardis A, et al; International Niemann-Pick Disease Registry (INPDR). Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018;13(1):50. doi:10.1186/s13023-018-0785-7 5. Burton BK, Ellis AG, Orr B, et al. Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States. Mol Genet Metab. 2021;134:182-187. doi:10.1016/j.ymgme.2021.06.011 6. Kassen S, Parseghian C, Andrews P, et al. Niemann-Pick Type C Patient and Caregiver Voices: Externally-led, Patient-focused Drug Development Meeting. The Ara Parseghian Medical Research Fund at Notre Dame; 2019.

Important Safety Information

Embryo-Fetal Toxicity

Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. The decision to continue or discontinue AQNEURSA treatment during pregnancy should consider the female’s need for AQNEURSA, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease.

Pregnancy and Lactation

For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA. Advise females of reproductive potential to use effective contraception during treatment with AQNEURSA and for 7 days after the last dose if AQNEURSA is discontinued.
There are no data on the presence of levacetylleucine or its metabolites in either human or animal milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AQNEURSA and any potential adverse effects on the breastfed infant from levacetylleucine or from the underlying maternal condition.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and greater than placebo) are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.

Drug Interactions

Avoid concomitant use of AQNEURSA with N-acetyl-DL-leucine or N-acetyl-D-leucine. The D-enantiomer, N-acetyl-D-leucine, competes with levacetylleucine for monocarboxylate transporter uptake, which may reduce the levacetylleucine efficacy.
Monitor more frequently for P-gp substrate related adverse reactions when used concomitantly with AQNEURSA; AQNEURSA inhibits P-gp; however, the clinical significance of this finding has not been fully characterized.

To report SUSPECTED ADVERSE REACTIONS, contact IntraBio Inc. at 1-833-306-9677 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indication

AQNEURSA^™ (levacetylleucine) is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg.

Please click here for Full Prescribing Information for AQNEURSA.

Niemann-Pick disease type C (NPC) is challenging to diagnose due to its heterogeneous symptoms of varying severity1,2

Diagnosis of NPC is often delayed and misdiagnosis is common in pediatric and adult patients1,2

Early diagnosis and proactive management of NPC can meaningfully benefit patients and their families1

Patients with NPC urgently need treatment that provides neurological and functional improvements1-3

Patients with NPC and their families would greatly benefit from a treatment option that improves neurological symptoms and provides functional benefits that are meaningful to their everyday lives1-3