Safety and effectiveness of MIPLYFFA (arimoclomol) were studied in 12-month multi-center, randomized, double-blind, placebo-controlled trial in patients with NPC, aged 2-19 years1
In Trial 1, 76% of patients in the MIPLYFFA group and 81% of those in the placebo group received miglustat as part of their routine clinical care.
Baseline demographics for subgroup of patients who also received miglustat (n=39)1
- Mean age was 11.6 years
- Mean time since first NPC symptom was 8.5 years
- Mean age at onset of first neurological symptom was 4.9 years
- Mean baseline in the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score was higher in the MIPLYFFA group (n=26; mean=8.9) than the placebo group (n=13; mean=7), with an overall mean R4DNPCCSS score of 8.311
The treatment effect in Trial 1 was assessed as change from baseline on the R4DNPCCSS
MIPLYFFA, in combination with miglustat, stopped disease progression at 12 months1
There were insufficient data to determine the effectiveness of the use of MIPLYFFA without miglustat for the treatment of neurological manifestations in patients with NPC.
MIPLYFFA is the first FDA-approved NPC treatment that has demonstrated long-term effectiveness of up to 5 years2
Consistent effectiveness in open-label extension (OLE)
In the 4-year OLE, the on-label population showed slower disease progression compared to the 1.9 points/year seen in the placebo group during the double-blind phase, supporting MIPLYFFA’s long-term effectiveness and durability for up to 5 years.
References
1. MIPLYFFA Full Prescribing Information. Celebration, FL, US, Zevra Therapeutics, Inc. ;09/2024
2. Mengel E, Da Riol RM, Del Toro M, et al. Long-term efficacy and safety of arimoclomol in Niemann-Pick disease type C: final results of the phase 2/3 NPC-002 48-month open-label extension trial. Mol Genet Metab. 2025;145(4):109189.
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
