HOW TO USE THIS SNAPSHOT

The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:

Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug. 

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the MIPLYFFA Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable). 

MIPLYFFA (arimoclomol) 
mye-PLYE-fah
Zevra Therapeutics Inc
Original Approval date: September 20, 2024

DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

MIPLYFFA is a prescription medicine that is used in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease, type C (NPC) in adults and children 2 years of age and older.

How is this drug used?

MIPLYFFA is a capsule that may be taken by mouth or given through a surgically placed feeding tube called a gastrostomy (G) tube, three times daily. 

Who participated in the clinical trials?

The FDA approved MIPLYFFA based on evidence from a clinical trial of 50 patients with NPC, 39 who were taking in combination with miglustat and included in labeling. The trial was conducted at 14 sites in Europe, Great Britain and the United States. Four patients were from the United States.

How were the trials designed?

MIPLYFFA was evaluated in one clinical trial of 50 patients with NPC. Study 1 was a randomized, multicenter, double-blind, placebo-controlled trial in patients with NPC. Patients 2 to 19 years of age were randomized 2:1 to receive MIPLYFFA at the recommended dose or placebo. The efficacy population included 39 patients who were also taking miglustat as part of their clinical care regimen. The efficacy endpoint was the change from baseline in the Rescored 4-Domain Niemann-Pick disease, Type C Clinical Severity Scale (R4DNPCCSS) at 12 months. The R4DNPCCSS is a measure of NPC disease progression that consists of four items assessing ambulation, speech, swallow and fine motor skills. 

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many males and females taking miglustat were enrolled in Study 1.

Figure 1. Baseline Demographics by Sex, Efficacy Population

Source: Adapted from FDA Review 

Figure 2 summarizes how many patients taking miglustat by race were enrolled in Study 1.

Figure 2. Baseline Demographics by Race, Efficacy Population 

Source: Adapted from FDA Review 

Figure 3 summarizes how many patients taking miglustat by age were enrolled in Study 1.

Figure 3. Baseline Demographics by Age, Efficacy Population 

Source: Adapted from FDA Review 

Figure 4 summarizes how many patients taking miglustat by ethnicity were enrolled in Study 1.

Figure 4. Baseline Demographics by Ethnicity, Efficacy Population 

Source: Adapted from FDA Review 

Who participated in the trials?

Table 1. Baseline Demographics of Participants Who Received Miglustat in Study 1 

Demographic MIPLYFFA
With Miglustat
N=26		 Placebo
With Miglustat
N=13		 Total
N=39
Age, years
Mean (SD) 12.8 (4.68) 9.08 (3.62) 11.6 (4.67)
Median (min, max) 14.0 (2.00, 19.0) 9.00 (3.00, 16.0) 11.0 (2.00, 19.0)
Age group, years, n (%)
≥12 16 (61.5) 2 (15.4) 18 (46.2)
<12 10 (38.5) 11 (84.6) 21 (53.8)
Sex, n (%)
Female 14 (53.8) 8 (61.5) 22 (56.4)
Male 12 (46.2) 5 (38.5) 17 (43.6)
Race, n (%)
Asian 1 (3.8) 1 (7.7) 2 (5.1)
Unknown 1 (3.8) 1 (7.7) 2 (5.1)
White 24 (92.3) 10 (76.9) 34 (87.2)
Native Hawaiian or other Pacific Islander 0 (0) 1 (7.7) 1 (2.6)
Ethnic, n (%)
Hispanic or Latino 2 (7.7) 0 (0) 2 (5.1)
Not Hispanic or Latino 24 (92.3) 13 (100) 37 (94.9)
Country, n (%)
Denmark 1 (3.8) 2 (15.4) 3 (7.7)
France 2 (7.7) 2 (15.4) 4 (10.3)
Germany 6 (23.1) 3 (23.1) 9 (23.1)
Italy 4 (15.4) 1 (7.7) 5 (12.8)
Spain 2 (7.7) 1 (7.7) 3 (7.7)
Switzerland 1 (3.8) 1 (7.7) 2 (5.1)
United Kingdom 7 (26.9) 2 (15.4) 9 (23.1)
United States 3 (11.5) 0 (0) 3 (7.7)
Poland 0 (0) 1 (7.7) 1 (2.6)

Source: Adapted from FDA Review
Abbreviations: SD, standard deviation

What are the benefits of this drug? 

In the clinical trial, clinicians rated patients’ symptoms based on the R4DNPCCSS. There was less worsening of symptoms after 12 months in patients with NPC who received MIPLYFFA in combination with miglustat than those who received placebo.

What are the benefits of this drug (results of trials used to assess efficacy)? 

Table 2. Mean Change From Baseline in R4DNPCCSS Score at Month 12 in Subgroup Who Received Miglustat 

Parameter MIPLYFFA
With Miglustat
N=26		 Placebo
With Miglustat
N=13		 Difference
(95% CI)
Mean R4DNPCCSS at baseline (SD) 8.9 (6.1) 7.0 (5.8)  
Mean Change in R4DNPCCSS (SE) at 12 monthsa -0.2 (0.5) 2.0 (0.7) -2.2 (-3.8, -0.6)

Source: Adapted from MIPLYFFA Prescribing Information
a Mean changes in R4DNPCCSS score from baseline to 12 months were estimated using an analysis of variance (ANCOVA) model fitted with treatment and baseline R4DNPCCSS score as covariate. 
Abbreviations: CI, confidence interval; R4DNPCCSS, Rescored Niemann-Pick disease Type C Clinical Severity Scale; SD, standard deviation; SE, standard error

Were there any differences in how well the drug worked in clinical trials among sex, race, and age? 

  • Sex: There was no notable difference in how well the drug worked between males and females.
  • Race: The number of patients of races other than White was small; therefore, differences in response to MIPLYFFA among races could not be determined. 
  • Age: MIPLYFFA was tested in patients with NPC between 2 and 19 years old. Any difference in how well the drug worked across age groups could not be determined because of limitations of the small sample size.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 3. Mean Change from Baseline in R4DNPCCSS Score at Month 12a by Sex Subgroup (Patients Who Received Miglustat) 

Sex MIPLYFFA With Miglustat Placebo With Miglustat  
  N Mean Change (SE) N Mean Change (SE) Difference (95% CI)
Female 14 0.0 (0.8) 8 2.5 (1.1) -2.5 (-5.3, 0.2)
Male 12 -0.5 (0.4) 5 1.3 (0.6) -1.8 (-3.1, -0.5)

Source: FDA Analysis
a Mean changes in R4DNPCCSS score from baseline to 12 months were estimated using an analysis of variance (ANCOVA) model fitted with treatment and baseline R4DNPCCSS score as covariate. 
Abbreviations: CI, confidence interval; R4DNPCCSS, Rescored Niemann-Pick disease type C Clinical Severity Scale; SE, standard error

What are the possible side effects?

MIPLYFFA may cause serious side effects such as hypersensitivity reactions and an increase in creatinine levels in the blood without affecting glomerular function.

The most common side effects are upper respiratory tract infections, diarrhea, and decreased weight. 

What are the possible side effects (results of trials used to assess safety)? 

Table 4. Adverse Reactions in ≥8% of Patients With NPC Treated With MIPLYFFA in Trial 1

Adverse Reaction MIPLYFFA With Miglustat 
N=26 
n (%)		 Placebo With Miglustat 
N=13 
n (%)
Upper respiratory tract infectiona 8 (31) 2 (15)
Diarrhea 6 (23) 3 (23)
Decreased weight 4 (15) 0
Decreased appetite 3 (12) 0
Tremor 3 (12) 0
Urticariab 3 (12) 0
Headache 3 (12) 1 (8)
Lower respiratory tract infection 3 (12) 1 (8)
Seizure 3 (12) 1 (8)

Source: Adapted from FDA Review
a Upper respiratory tract infection: Combined incidence of upper respiratory tract infection and rhinitis. 
b Urticaria: Includes one patient in which urticaria occurred alone (3%) and two patients who had urticaria with angioedema (6%)
Abbreviations: NPC, Niemann-Pick disease type C

Were there any differences in side effects among sex, race, and age?

  • Sex: In this small trial size, a difference in side effects between males and females could not be determined. 
  • Race: The number of patients in the clinical trial was small, and the majority of patients were White; therefore, differences in side effects to MIPLYFFA among races could not be determined.
  • Age: MIPLYFFA was tested in patients with NPC ages 2 through 19 and similar side effects occurred across age groups.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.

COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.

EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.

PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.