Drug Trials Snapshots: ELFABRIO
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 ELFABRIO 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).
ELFABRIO (pegunigalsidase alfa-iwx)
Chiesi Farmaceutici S.p.A.
Original Approval date: May 9, 2023
DRUG TRIALS SNAPSHOT SUMMARY
What is the drug for?
ELFABRIO is an enzyme replacement therapy that is used for the treatment of Fabry disease in adult patients. Fabry disease is an inherited disorder that occurs when the enzyme alpha-galactosidase-A is deficient, affecting the breakdown of a type of fat called globotriaosylceramide (Gb3) in various tissues of the body such as the kidney, heart, brain, nerves, and digestive system.
How is this drug used?
ELFABRIO is administered by a healthcare provider using a needle placed in a vein (known as an intravenous infusion) every two weeks.
Who participated in the clinical trials?
ELFABRIO’s safety and efficacy data came from two clinical trials. Trial 1, evaluating efficacy, enrolled 16 Fabry disease patients who had never previously received enzyme replacement therapy or who had not received enzyme replacement therapy for more than 26 weeks prior to study entry. Trial 2, evaluating safety, enrolled 77 Fabry disease patients who had previously been treated with enzyme replacement therapy (agalsidase beta). Trial 1 was conducted at 13 study sites from 6 countries; Trial 2 was conducted at 28 study sites from 12 countries.
How were the trials designed?
Trial 1, designed to identify optimal dose and evaluate efficacy, enrolled 16 Fabry disease patients who had never previously received enzyme replacement therapy or who had not received enzyme replacement therapy for more than 26 weeks prior to study entry. Trial 2, designed the evaluate safety, enrolled 77 Fabry disease patients who had previously been treated with enzyme replacement therapy (agalsidase beta).
In Trial 1, patients received ELFABRIO at doses of either 0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg intravenously once every two weeks. The approved dose is 1.0 mg/kg. The efficacy and safety of the 0.2 mg/kg and 2.0 mg/kg have not been established and are not approved or recommended. The study endpoint was assessed six months following treatment initiation. There was no comparator group in Trial 1. In Trial 2, patients received ELFABRIO intravenously once every two weeks for 24 months. The comparator group in Trial 2 was agalsidase beta.
The benefit of ELFABRIO in Trial 1 was evaluated by assessing the amount of Gb3 deposition in the kidneys assessed by renal biopsy. Trial 2 evaluated the effects of ELFABRIO on safety and tolerability and also on estimated glomerular filtration rate (a measure of kidney function).
How were the trials designed?
Trial 1 was a single arm study that enrolled Fabry disease subjects who had never previously received enzyme replacement therapy or who had not received enzyme replacement therapy for more than 26 weeks prior to study entry. Trial 2 was a randomized, double-blind, active-controlled study versus agalsidase beta in Fabry disease subjects who were receiving enzyme replacement therapy at time of study entry.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy and safety of ELFABRIO.
Figure 1. Baseline Demographics by Sex, Combined Efficacy and Safety Populations
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race enrolled in the combined clinical trials used to evaluate the efficacy and safety of ELFABRIO.
Figure 2. Baseline Demographics by Race, Combined Efficacy and Safety Populations
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age enrolled in the combined clinical trials used to evaluate the efficacy and safety of ELFABRIO.
Figure 3. Baseline Demographics by Age, Combined Efficacy and Safety Populations
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity enrolled in the combined clinical trials used to evaluate the efficacy and safety of ELFABRIO.
Figure 4. Baseline Demographics by Ethnicity, Combined Efficacy and Safety Populations
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Demographics Table, Combined Efficacy and Safety Populations1
| Characteristic | Total Population N=93 |
| Sex, n (%) | |
| Male | 56 (60.2) |
| Female | 37 (39.8) |
| Age, years | |
| Mean (SD) | 42.4 (11.2) |
| Median (min, max) | 44 (17, 60) |
| Age group, years, n (%) | |
| <18 | 1 (1.1) |
| ≥18 | 92 (98.9) |
| Race, n (%) | |
| Asian or Pacific Islander | 2 (2.2) |
| Black or African American | 6 (6.5) |
| White | 84 (90.3) |
| Other | 1 (1.1) |
| Ethnicity, n (%) | |
| Hispanic or Latino | 5 (5.4) |
| Not Hispanic or Latino | 88 (94.6) |
| Country of participation, n (%) | |
| United states | 63 (67.7) |
| United Kingdom | 6 (6.5) |
| Spain | 5 (5.4) |
| Netherlands | 5 (5.4) |
| Other | 14 (15.1) |
Source: Adapted from FDA Review
1 The combined population contains 16 patients from Trial 1 who were all treated with ELFABRIO and 77 patients from Trial 2, of which 52 were treated with ELFABRIO.
Abbreviations: SD, standard deviation
What are the benefits of this drug?
ELFABRIO reduced the amount of Gb3 deposited in kidney tissue of adult Fabry patients after six months of treatment. Reduction of Gb3 deposits in the kidney, for example, is expected to slow the rate of progression of kidney disease.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Summary of the Renal Biopsy BLISS Score1 of Gb3 Inclusions at Baseline and After 26 Weeks of ELFABRIO Treatment in Adults With Fabry Disease (Trial 1)
| Median (Range) | All Patients N=14 |
Males N=8 |
Females N=6 |
| Baseline | 3.2 (0.4, 9.0) | 6.8 (0.4, 9.0) | 1.2 (0.8, 3.3) |
| Week 26 | 0.7 (0.3, 2.5) | 0.7 (0.3, 2.5) | 0.7 (0.3, 1.4) |
| Change at Week 26 | -2.5 (-8.5, 0.5) | -5.3 (-8.5, 0.5) | -0.7 (-2.5, 0.1) |
| Mean change at Week 26 (95% CI) | -3.1 (-4.8, -1.4) | -4.7 (-7.1, -2.3) | -1.0 (-2.1, 0.1) |
Source: Adapted from ELFABRIO Prescribing Information
1 The BLISS methodology counts the number of Gb3 inclusions in each renal PTC contained in a biopsy specimen. For each biopsy specimen (slide), approximately 300 renal PTCs were scored, and the final biopsy score for each patient was determined as the average number of Gb3 inclusions per PTC.
Abbreviations: BLISS, Barisoni Lipid Inclusion Scoring System; CI, confidence interval; Gb3, globotriaosylceramide; PTC, peritubular capillary
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
The number of patients in the trial was too small to determine if there were differences in how well the drug worked based on sex, race, or age.
What are the possible side effects?
ELFABRIO may cause serious side effects such as hypersensitivity reactions and infusion-associated reactions.
The most common side effects are infusion-associated reactions, nasal and throat irritation (nasopharyngitis), headache, diarrhea, fatigue, nausea, back pain, pain in arms or legs, joint pain (arthralgia), and sinus infection.
What are the possible side effects (results of trials used to assess safety)?
Table 3 summarizes adverse reactions in patients with Fabry disease previously treated with agalsidase beta prior to study entry and who upon study entry were randomly assigned to received either ELFABRIO or comparator (agalsidase beta) for 24 months.
Table 3. Adverse Reactions in Adults With Fabry Disease (Trial 2)1
| Adverse Reaction | ELFABRIO N=52 n (%) |
Agalsidase Beta N=25 n (%) |
| Infusion-associated reaction2,4 | 17 (32) | 8 (32) |
| Nasopharyngitis | 11 (21) | 4 (16) |
| Headache | 11 (21) | 5 (20) |
| Diarrhea | 10 (19) | 6 (24) |
| Fatigue | 9 (17) | 4 (16) |
| Nausea | 9 (17) | 3 (12) |
| Back pain | 8 (15) | 5 (20) |
| Pain in extremity | 8 (15) | 4 (16) |
| Sinusitis | 8 (15) | 3 (12) |
| Abdominal pain | 6 (12) | 0 (0) |
| Proteinuria | 6 (12) | 0 (0) |
| Hypersensitivity3,4 | 5 (9) | 4 (16) |
| Upper respiratory tract congestion | 4 (8) | 0 (0) |
| Neuralgia | 4 (8) | 0 (0) |
| Peripheral neuropathy | 3 (6) | 0 (0) |
| Sciatica | 3 (6) | 0 (0) |
| Infusion site extravasation | 3 (6) | 0 (0) |
| Hematuria | 3 (6) | 0 (0) |
Source: ELFABRIO Prescribing Information
1 Adverse reactions were those that occurred in ≥5% of ELFABRIO-treated patients.
2 Infusion-associated reaction includes: nausea, vomiting, abdominal pain, diarrhea, fatigue, chills, malaise, non-cardiac chest pain, hypersensitivity, body temperature increased, burning sensation, neuralgia, agitation, throat irritation, pruritic rash, and flushing. Events occurring within 24 hours.
3 Hypersensitivity includes: macular rash, pruritic rash, and face swelling. Events occurring within 24 hours.
4 The events of hypersensitivity and pruritic rash fall in both hypersensitivity and infusion-associated reaction categories.
Were there any differences in side effects among sex, race, and age?
- Sex: The number of participants enrolled in the trials were too small to determine if side effects differed between males and females.
- Race: The number of patients of races other than White was small; therefore, differences side effects among races could not be determined.
- Age: No patients older than 65 years of age were included, therefore, the differences in occurrence of side effects been patients younger and older than 65 years of age could not be determined.
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.