Drugs

Drug Trials Snapshots: GALAFOLD

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age 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 health provider about the risks and benefits of a drug. Refer to the GALAFOLD Package Insert for complete information.

GALAFOLD (migalastat hydrochloride)
gal-a-fold
Amicus Therapeutics U.S., Inc.
Approval date: August 10, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

GALAFOLD is a drug for treatment of Fabry disease in adults. It is used in patients who have a specific change in the gene that causes Fabry disease. Change in the gene causes the corresponding enzyme to be a good target for therapy with GALAFOLD based on laboratory data.

Fabry disease is a rare, inherited disease that results from buildup of fat deposits called globotriaosylceramide (GL-3) in the body’s cells (including blood vessels and kidney) because of decreased activity of an enzyme called alpha galactosidase A (GLA).

How is this drug used?

GALAFOLD is taken as a capsule by mouth once every other day.

What are the benefits of this drug?

After six months of treatment, patients treated with GALAFOLD had a greater decrease in fat deposits in blood vessels of the kidney when compared to patients on placebo.

GALAFOLD was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug for serious condition while the company continues to conduct clinical trials to confirm that the drug works well.

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

The table below summarizes efficacy results for the evaluated patients for Trial 1.

Table 2. Changes from Baseline to Month 6 in Average Number of GL-3 Inclusions per Kidney Interstitial Capillary (KIC) in Adults with Fabry Disease with Amenable GLA Variants in Trial 1 (N = 45)

 GALAFOLD

n/N (%) with ≥ 50% reduction
Median change from baseline (range)
Placebo

n/N (%) with ≥ 50% reduction
Median change from baseline (range)
All patients (N = 45)13/25 (52%)
-0.04 (-1.94, 0.26)
9/20 (45%)
-0.03 (-1.00, 1.69)
Females (N = 29)8/18 (44%)
-0.02 (-0.46, 0.26)
5/11 (46%)
-0.03 (-0.35, 0.10)
Males (N = 16)5/7 (71%)
-1.10 (-1.94, -0.02)
4/9 (44%)
-0.03 (-1.00, 1.69)
Patients with baseline GL‑3 ≥ 0.3 (N = 17; 9 males, 8 females)7/9 (78%)
-0.91 (-1.94, 0.19)
2/8 (25%)
-0.02 (-1.00, 1.69)
Patients with baseline GL‑3 < 0.3 (N = 28; 7 males, 21 females)6/16 (38%)
-0.02 (-0.10, 0.26)
7/12 (58%)
-0.05 (-0.16, 0.14)

In Trial 1, patients with non-amenable GLA variants (n = 17) had no change from baseline in the average number of GL-3 inclusions per KIC after 6 months of treatment.

GALAFOLD Prescribing Information

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

  • Sex: GALAFOLD appeared to work better in males than in females.
  • Race: The majority of patients in the trial was White. Differences in how the drug works among races could not be determined.
  • Age: The majority of patients in the trial was 18-65 years of age. Differences in how the drug works among different age groups could not be determined.

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

Efficacy results by sex are replicated below. Analyses of subgroups by race and age were not conducted because the majority of patients was White and less than 65 years of age.

Table 3. Changes from Baseline to Month 6 in Average Number of GL-3 Inclusions per Kidney Interstitial Capillary (KIC) in Adults with Fabry Disease with Amenable GLA Variants in Trial 1 (N = 45)

GroupGALAFOLD
n/N (%) with ≥ 50% reduction
Median change from baseline (range)
Placebo
n/N (%) with ≥ 50% reduction
Median change from baseline (range)
ITT-amenable AH patients (N = 45)13/25 (52%)
-0.04 (-1.94, 0.26)
9/20 (45%)
-0.03 (-1.00, 1.69)
Females (N = 29)8/18 (44%)
-0.02 (-0.46, 0.26)
5/11 (46%)
-0.03 (-0.35, 0.10)
Males (N = 16)5/7 (71%)
-1.10 (-1.94, -0.02)
4/9 (44%)
-0.03 (-1.00, 1.69)

GALAFOLD Prescribing Information

What are the possible side effects?

The most common side effects are headache, nasal and throat irritation (nasopharyngitis), urinary tract infection, nausea, and fever (pyrexia).

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

The table below summarizes adverse reactions in patients with Fabry disease who were naïve to GALAFOLD and enzyme replacement therapy or were not treated with enzyme replacement therapy for at least 6 months (safety population).

Table 4. Adverse Reactions* Reported During the First 6 Months of Treatment in Patients with Fabry Disease in Trial 1.

Adverse ReactionGALAFOLD
%
(N = 34)
Placebo
%
(N = 33)
Headache35%21%
Nasopharyngitis18%6%
Urinary tract infection**15%0
Nausea12%6%
Pyrexia12%3%
Abdominal pain9%3%
Back pain9%0
Cough9%0
Diarrhea9%3%
Epistaxis9%3%

* reported in at least 5% of patients treated with GALAFOLD and at a higher rate than placebo
** included urinary tract infection, cystitis, and kidney infection

GALAFOLD Prescribing Information

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

  • Sex: The occurrence of side effects was similar among males and females with the exception of urinary tract infection which was seen more frequently in females than in males.
  • Race: The majority of patients in the trial was White. Differences in the occurrence of side effects among races could not be determined.
  • Age: The majority of patients in the trial was 18-65 years of age. Differences in the occurrence of side effects among different age groups could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The tables below summarize the occurrence of adverse reactions, headache and urinary tract infections (UTI) by sex. Analyses of subgroups by race and age were not conducted because the majority of patients was White and less than 65 years of age.

Table 5. Pooled Subgroup Analysis of Headache by Sex (safety population)

Demographic CharacteristicGALAFOLD
n/N (%)
Placebo
n/N (%)
Sex
Male4/12 (33)3/12 (25)
Female8/22 (36)4/21 (19)

Clinical Trial Data

Table 6. Pooled Subgroup Analysis of UTI by Sex (safety population)

Demographic CharacteristicGALAFOLD
n/N (%)
Placebo
n/N (%)
Sex
Male1/12 (8)0/12 (0)
Female4/22 (18)0/21 (0)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved GALAFOLD based primarily on evidence from one clinical trial (NCT00925301/Trial 1) of 67 adults with Fabry disease. The trial was conducted at 13 sites in Canada, Europe, Latin America, and the United States.

All 67 patients were evaluated for side effects (safety population) and are presented below. Out of these 67 patients, 45 patients were evaluated for benefit (efficacy population) and are presented in Table 8, under the MORE INFO section.

Figure 1 summarizes the percentage of patients by sex in the clinical trial.

Figure 1. Baseline Demographics by Sex (safety population)

Pie chart summarizing how many males and females were in the clinical trials. In total, 24 males (36%) and 43 females (64%) participated in the clinical trial.

FDA Review

Figure 2 summarizes the percentage of patients by race in the clinical trial.

Figure 2. Baseline Demographics by Race (safety population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 65 White (97%) and 2 Other patients (3%) participated in the clinical trial.

FDA Review

Table 1. Baseline Demographics by Race (safety population)

RaceNumber of PatientsPercentage of Patients
White6597%
Other23%

FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trial used to evaluate safety.

Figure 3. Baseline Demographics by Age (safety population)

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trials. In total, 66 patients (99%) were less than 65 years old, and 1 patient (1%) was 65 years and older.

FDA Review

Who participated in the trials?

The table below summarizes demographics of all patients in the clinical trial.

Table 7. Baseline Characteristics (safety population)

Demographic ParameterGALAFOLD
N = 34
Placebo
N = 33
Total
N = 67
Sex, n (%)
Male12 (35)12 (36)24 (36)
Female22 (65)21 (64)43 (64)
Race, n (%)
White32 (94)33 (100)65 (97)
Other2 (6)0 (0)2 (3)
Age Group, n (%)
<65 years33 (97)33 (100)66 (99)
> 65 years1(3)0 (0)1 (1)
Age (Mean Years +SD)40 + 13.344 + 10.242 + 11.8
Ethnicity, n (%)
Hispanic1 (3)3 (3)4 (6)
Not Hispanic9 (26)14 (27)23 (34)
Missing24 (71)16 (49)40 (60)
Region, n (%)
Canada2 (6)1 (3)3 (4)
United States10 (29)10 (30)20 (30)
Europe19 (56)18 (55)37 (55)
Latin America3 (9)4 (12)7 (10)

Clinical Trial Data

The table below summarizes demographics of all patients in the efficacy population.

Table 8. Baseline Characteristics for the Intent-to-Treat Amenable Population (efficacy population)

Demographic ParameterGALAFOLD
N = 25
Placebo
N = 20
Total
N = 45
Sex, n (%)
Male7 (28)9 (45)16 (36)
Female18 (72) 11 (55) 29 (64)
Race, n (%)
White23(92)20 (100)43 (96)
Other2 (8)0 (0)2 (4)
Age Group, n (%)
<65 years24 (96)20 (100)44 (98)
> 65 years1 (4)0 (0)1 (2)
Age Mean Years +SD)43 + 1345 + 844 + 11
Ethnicity, n (%)
Hispanic0 (0)3 (15)3 (7)
Not Hispanic15 (60)7 (35)22 (49)
Missing10 (40)10 (50)20 (44)
Region, n (%)
Australia3 (12)4 (20)7 (16)
Canada2 (8)0 (0)2 (4)
United States6 (24)5 (25)11 (24)
Europe12 (48)8 (40)20 (44)
Latin America2 (8)3 (15)5 (11)

Clinical Trial Data

How were the trials designed?

The benefit and side effects of GALAFOLD were evaluated primarily in one clinical trial. Trial 1 enrolled adults with Fabry disease who had a genetic change and corresponding enzyme change. The enzyme change was determined to be a good target for therapy with GALAFOLD based on laboratory data. The patients never received treatment to replace the missing enzyme or had not received treatment to replace the missing enzyme for at least 6 months. Patients were randomly assigned to receive GALAFOLD or placebo once every other day for 6 months. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed.

The benefit of GALAFOLD was assessed after 6 months of treatment, by determining the number of fat deposits (GL-3) in blood vessel cells of the kidneys (by kidney biopsy). The proportion of patients with a 50% or more reduction in the average number of fat deposits (GL 3) after receiving GALAFOLD was compared to the proportion of patients with a 50% or more reduction in the average number of fat deposits (GL 3) after receiving the placebo.

How were the trials designed?

The safety and efficacy of GALAFOLD were established primarily based on one randomized, double-blind, placebo-controlled trial of 6 months’ duration. Patients with Fabry disease who were naïve to GALAFOLD and enzyme replacement therapy or were not treated with enzyme replacement therapy for at least 6 months were evaluated. Patients received GALAFOLD or placebo capsule every other day for 6 months.

The primary efficacy outcome measure was the average number of GL-3 inclusions per kidney interstitial capillary (KIC) as assessed by light microscopy of kidney biopsy samples before and after 6 months of treatment.

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.

PRESCRIBING INFORMATION

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Page Last Updated: 09/06/2018
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