NPC is an ultra-rare, relentlessly progressive neurodegenerative disease1
- NPC is a genetic disease that leads to dysfunctional NPC proteins1
- In NPC, the accumulation of unprocessed lipids leads to dysfunction in the brain, liver, and spleen1,2
- NPC is difficult to diagnose, and can affect patients at any ages1,3
- Patients aged >15 years could represent up to one-third of all patients with NPC4
Symptoms of NPC are progressive and may present differently depending on age1
Accurate diagnosis is critical for early intervention
Types of tests:
- oxysterols
- lysosphingolipids*
- bile acids
In addition, a medical history and clinical examination can aid in proper diagnosis. NPC is not curable, but management with available treatments is possible.1,3
†No longer standard and only used as confirmatory evidence following inconclusive genetic testing.
Evaluating NPC can be challenging1,2,4,5
Diagnosis of NPC can be elusive due to its heterogeneous clinical presentation. As a result of its symptom variability and onset, there are often delays in diagnosis of NPC. Accurate diagnosis is critical for early intervention and effective management with the goal of delaying progression.
Once diagnosed, using a validated scale to measure NPC progression is important4,6
A predictive model and scoring system for NPC has been developed to help clinicians assess disease burden, disease progression, stabilization with therapy, and prognosis. The consistent framework of a validated clinician reported scale, created specifically for NPC, provides a reliable and objective system that demonstrates treatment efficacy.4
References
1. Mengel E, et al. Impacts and burden of Niemann pick type-C: a patient and caregiver perspective. Orphanet J Rare Dis. 2021;16(1):493. 2. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5(16):1-18. 3. Patterson MC, Clayton, Gissen P, et al. Recommendations for the detection and diagnosis of Niemann-Pick disease type C: an update. Neurol Clin Pract. 2017;7(6):499-511. 4. Geberhiwot T, Moro A, Dardis A, et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018;13(1):1-19. 5. Mengel E, Klünemann HH, Lourenço CM, et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis. 2013;8:166. 6. Evans W, Patterson M, Platt F, Guldberg C, Matheson T, Pacey J. International consensus on clinical severity scale use in evaluating Niemann–Pick disease Type C in pediatric and adult patients: results from a Delphi Study. Orphanet J Rare Dis. 2021;16(1):115.
MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older.
Hypersensitivity Reactions: Hypersensitivity reactions such as urticaria and angioedema have been reported in patients treated with MIPLYFFA during Trial 1: two patients reported both urticaria and angioedema (6%) and one patient (3%) experienced urticaria alone within the first two months of treatment. Discontinue MIPLYFFA in patients who develop severe hypersensitivity reactions. If a mild or moderate hypersensitivity reaction occurs, stop MIPLYFFA and treat promptly. Monitor the patient until signs and symptoms resolve.
Embryofetal Toxicity: MIPLYFFA may cause embryofetal harm when administered during pregnancy based on findings from animal reproduction studies. Advise pregnant females of the potential risk to the fetus and consider pregnancy planning and prevention for females of reproductive potential.
Increased Creatinine without Affecting Glomerular Function: Across clinical trials of MIPLYFFA, mean increases in serum creatinine of 10% to 20% compared to baseline were reported. These increases occurred mostly in the first month of MIPLYFFA treatment and were not associated with changes in glomerular function.
During MIPLYFFA treatment, use alternative measures that are not based on creatinine to assess renal function. Increases in creatinine reversed upon MIPLYFFA discontinuation.
The most common adverse reactions in Trial 1 (≥15%) in MIPLYFFA-treated patients who also received miglustat were upper respiratory tract infection, diarrhea, and decreased weight.
Three (6%) of the MIPLYFFA-treated patients had the following adverse reactions that led to withdrawal from Trial 1: increased serum creatinine (one patient), and progressive urticaria and angioedema (two patients). Serious adverse reactions reported in MIPLYFFA-treated patients were hypersensitivity reactions including urticaria and angioedema.
To report SUSPECTED ADVERSE REACTIONS, contact Zevra Therapeutics, Inc. at toll-free phone 1-844-600-2237 or FDA at 1 800-FDA-1088 or www.fda.gov/medwatch.
Drug Interaction(s): Arimoclomol is an inhibitor of the organic cationic transporter 2 (OCT2) transporter and may increase the exposure of drugs that are OCT2 substrates. When MIPLYFFA is used concomitantly with OCT2 substrates, monitor for adverse reactions and reduce the dosage of the OCT2 substrate.
Use in Females and Males of Reproductive Potential: Based on animal findings, MIPLYFFA may impair fertility and may increase post-implantation loss and reduce maternal, placental, and fetal weights.
Renal Impairment: The recommended dosage of MIPLYFFA, in combination with miglustat, in patients with an eGFR ≥15 mL/minute to <50 mL/minute is lower than the recommended dosage (less frequent dosing) in patients with normal renal function.
MIPLYFFA capsules for oral use are available in the following strengths: 47 mg, 62 mg, 93 mg, and 124 mg.
Before prescribing MIPLYFFA, please read the full Prescribing Information, including Instructions for Use
