Using a validated scale for NPC in clinical practice
The NPC Clinical Severity Scale (NPCCSS) is a clinician-reported outcome measure of disease severity and progression.1 It was developed specifically for use in evaluating NPC.2 The credibility of this scale was established through clinical trial data to provide validity and help assess clinically meaningful change.3
When assessing treatment effectiveness for NPC, focus on changes across the domains that were identified as most important by NPC expert clinicians, patients, and caregivers.3
Applying the NPCCSS domain
The validated scale originally included 17 domains to assess clinical severity. However, its complexity can be challenging to implement in everyday practice. Additionally, several domains, such as seizures, gelastic cataplexy, and psychiatric symptoms, have the potential to be confounded by symptomatic treatment interventions.2
The 5-domain NPCCSS is simpler, and quicker to administer and complete in a routine clinical exam while still being reliable.4
- Was validated using a wide range of disease severities1
- Was demonstrated by clinical study to include the domains most relevant to NPC clinicians, patients, and caregivers1
- Allows a comprehensive assessment of the symptom burden experienced by NPC patients1
- The cognition domain was removed from the 5-domain NPCCSS and the swallow domain was rescored to more accurately measure progressive deterioration of the swallow function5
- Swallow, along with ambulation and speech, was seen as a highly salient sign of disease progression by healthcare providers, caregivers, and patients5
References
1. Patterson MC, Lloyd-Price L, Guldberg C, et al. Validation of the 5‑domain Niemann‑Pick type C Clinical Severity Scale. Orphanet J Rare Dis. 2021;16(1):79. 2. Mengel et al. Clinical disease progression and biomarkers in Niemann–Pick disease type C: a prospective cohort study. Orphanet J Rare Dis. 2020;15:328 3. Patterson MC, Lloyd-Price L, Guldberg C, et al. Validation of the 5‑domain Niemann‑Pick type C Clinical Severity Scale. Orphanet J Rare Dis. 2021;16(1):79. 4. 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. 5. Mengel E. Efficacy results from a 12-month double-blind randomized trial of arimoclomol for treatment of Niemann-Pick disease type C (NPC): presenting a rescored 4-domain NPC Clinical Severity Scale. Mol Genet Metab. (Submitted manuscript) 6. Berry-Kravis EM, LaGorio L, Dali C, Gallo D. Qualitative assessment of the validity and standardization of the Swallow domain in the 5-domain Niemann-Pick disease type C (NPC) Clinical Severity Scale (5DNPCCSS). Poster presented at: WORLD; February 3-7, 2025; San Diego, CA.
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
