Last updated May 11, 2023, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD
What is Elfabrio for Fabry disease?
Elfabrio (pegunigalsidase alfa) is an enzyme replacement therapy (ERT) approved for adults with Fabry disease. The therapy, formerly PRX-102, was developed by Protalix BioTherapeutics and Chiesi Global Rare Diseases.
It was authorized by the European Commission for treating adults with Fabry disease in May 2023. Days later, it was approved in the U.S. for the same indication.
How does Elfabrio work?
Fabry disease is caused by mutations in the GLA gene, which provides instructions for making alpha-galactosidase A (Gal A), an enzyme needed to break down certain fatty molecules. Without a functional version of this enzyme, these fatty molecules build up to toxic levels in cells, causing tissue damage and leading to Fabry symptoms.
As an enzyme replacement therapy, Elfabrio is intended to deliver a working version of the Gal A enzyme to cells. It contains a version of the enzyme made with Protalix’s plant-based ProCellEx platform with a specific chemical modification called PEGylation. This version is designed to be more stable than those used in older ERTs and provide a long half-life, the time required for the blood level of a medication to reduce by half.
Who can use Elfabrio?
Elfabrio is indicated for treating adults with confirmed Fabry disease.
Who should not use Elfabrio?
There are no contraindications for Elfabrio’s use. However, if a patient given Elfabrio has a severe infusion or allergic reaction to the medication, it should be immediately discontinued. According to the boxed warning in Elfabrio’s prescribing label, appropriate medical support measures, such as cardiopulmonary resuscitation equipment, should be readily available in case a severe hypersensitivity reaction occurs. Appropriate treatment should be initiated.
How is Elfabrio administered?
Elfabrio is administered every other week via an infusion into the bloodstream. It’s given at a dose of 1 milligram (mg) per kilogram (kg) of body weight. Before each infusion, patients may be treated with anti-inflammatory medications like antihistamines or corticosteroids to reduce the risk of allergic reactions.
For the first few infusions, the infusion rate (the speed at which the medication is administered) is determined based on the patient’s body weight. Slower infusion rates are used for patients who’ve never been on an enzyme replacement therapy before starting Elfabrio. Those who’ve previously been on an ERT can start at slightly higher rates.
If a patient experiences mild or moderate infusion reactions, the infusion may be paused for 15 to 30 minutes and the infusion rate may be slowed by 25% to 50%. If the reaction persists despite pausing and slowing treatment, the infusion should be stopped and the patient should be monitored. A new infusion may be given a week or two later at a slower infusion rate and with appropriate pretreatment to manage infusion reactions.
If the first four to six infusions are tolerated well, subsequent infusions can be shortened. It’s recommended that the total infusion time be reduced by 30 minutes every third infusion, down to a minimum infusion time of 1.5 hours.
If a scheduled dose is missed, an infusion should be given as soon as possible and then every two weeks thereafter. The dose shouldn’t be increased to compensate for missed infusions.
Elfabrio in clinical trials
Elfabrio has been assessed in three Phase 3 clinical trials called BRIDGE, BALANCE, and BRIGHT.
BRIDGE trial in patients previously on Replagal
The BRIDGE study (NCT03018730) enrolled 22 adults with Fabry (15 men, seven women) who’d been on stable treatment with Replagal (agalsidase alfa), an older Fabry ERT sold by Takeda, for at least two years before entering the study. Participants were screened for three months while on Replagal then switched to Elfabrio, given via infusion every two weeks for about one year.
Switching therapies was generally well tolerated, results showed. Five patients had treatment-related side effects and two discontinued Elfabrio due to side effects (specifically immune reactions against the therapy).
Findings also suggested Elfabrio slowed the decline in kidney function, as assessed with a measure called estimated glomerular filtration rate, or eGFR. This measure is calculated in mL per minute per 1.73 meters squared.
With Replagal, the average eGFR score worsened by 5.9 per year. By contrast, the mean rate of eGFR worsening was 1.19 per year over a year on Elfabrio, with 60% of patients showing stable kidney function with it.
Data also suggested Elfabrio reduced levels of the Fabry disease biomarker globotriaosylsphingosine (lyso-Gb3), by 31.5% on average. The decrease in lyso-Gb3 was more pronounced among men, who generally had higher levels of this biomarker going into the trial.
BALANCE trial comparing against Fabrazyme
The BALANCE study (NCT02795676) enrolled 78 adults with Fabry and impaired kidney function, all who’d previously been treated with Fabrazyme (agalsidase beta) — an approved ERT sold by Sanofi Genzyme — for at least a year.
The participants were randomly assigned to continue on Fabrazyme or switch to Elfabrio for about two years. Both therapies were given via infusion every two weeks at a dose of 1 mg/kg.
Top-line results showed both therapies had comparable effects on kidney function. After two years, the median eGFR worsened by 2.514 for patients on Elfabrio and 2.155 with Fabrazyme.
Safety data also were comparable. The side effects of treatment were reported in about 40% of patients on either therapy. Six patients discontinued the study, including one due to a side effect of Elfabrio.
BRIGHT study testing less frequent dosing
The BRIGHT trial (NCT03180840) enrolled 30 adults with Fabry disease (24 men, six women) who’d been on stable treatment with an approved ERT (Fabrazyme or Replagal), given via infusion every other week, for at least three years.
In BRIGHT, the patients were switched to Elfabrio at a dose of 2 mg/kg via infusion every four weeks. One patient withdrew from the study early as a result of a traffic accident. Of the 29 patients who stayed for at least a year, almost all maintained the less-frequent dosing regimen except for one who was switched to 1 mg/kg given every two weeks due worsening clinical condition.
Top-line data showed relatively stable kidney function with once-monthly Elfabrio. The average rate of eGFR worsening was 1.27. Levels of the disease biomarker lyso-Gb3 also were generally stable with less-frequent Elfabrio dosing, with mean levels increasing from 19.36 nanomolar (nM) at the study’s start to 22.23 nM after a year. There were no substantial Fabry-related clinical events reported during the study.
Patients’ self-rated quality of life — measured on a scale from 0 to 100 using the Quality of Life EQ-5D-5L questionnaire — was generally good at the start of the trial, with a mean score of 78.3. After one year in the study, average quality of life scores remained high at 82.1. Based on responses to the short-form Brief Pain Inventory (BPI) questionnaire, three-quarters (75%) of patients had no pain worsening after a year in BRIGHT.
Common side effects of Elfabrio
The most common side effects related to Elfabrio treatment in clinical trials include:
- sinus inflammation (sinusitis) and the common cold (nasopharyngitis)
- headache
- fatigue
- diarrhea
- nausea
- pain in the back and/or limbs
Patients also may have infusion-associated reactions (IARs), which occur during or shortly after Elfabrio is administered. These may include:
- nausea
- vomiting
- abdominal pain
- diarrhea
- fatigue
- chills
- general feelings of discomfort or being unwell (malaise)
- burning sensations
- chest pain unrelated to the heart
- increased body temperature
- nerve pain (neuralgia)
- agitation
- throat irritation
- itchy skin
- flushing
- shortness of breath
Infusion-associated reactions
Hypersensitivity reactions, meaning exaggerated or inappropriate immune responses, were reported in 14% of patients given Elfabrio in clinical trials. The risk of allergic reaction may be increased in patients who are positive for antibodies targeting the enzyme. If mild or moderate reactions occur, the infusion may be paused or slowed.
Severe allergic reactions, known as anaphylaxis, have been reported in patients given Elfabrio. If a severe anaphylactic reaction occurs, the medication should immediately be discontinued, and appropriate support should be given.
Kidney damage
A case of membranoproliferative glomerulonephritis — a potentially severe form of kidney damage — was reported in a patient given Elfabrio in a clinical trial. Markers of kidney function should be regularly monitored with Elfabrio and the therapy should be discontinued until a full kidney evaluation can be performed if a patient shows signs of kidney damage.
Use in pregnancy and breastfeeding
There are no available data in people about using Elfabrio during pregnancy or breastfeeding. As an enzyme replacement therapy, Elfabrio is not expected to cause problems during pregnancy, however. Studies in animal models have generally shown no problematic effects on embryonic development (apart from low fetal body weight) when Elfabrio is given at doses more than three times higher than what’s used with Fabry disease.
A registry study is collecting data for people with Fabry disease who become pregnant while on Elfabrio. Healthcare providers can report data to the registry by phone at 1-888-661-9260 or online.
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