Enzyme replacement therapy for Pompe disease
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Enzyme replacement therapy, commonly abbreviated as ERT, is an approved treatment strategy used in Pompe disease. ERTs are currently the only approved treatments for Pompe that address the condition’s underlying cause. By replacing needed enzymes, the therapy works to reduce and slow the progression of muscle wasting and heart problems that characterize Pompe disease.
How does ERT work?
Pompe disease is an inherited disorder caused by mutations in the gene that provides instructions for making an enzyme called acid alpha-glucosidase, or GAA. This enzyme normally breaks down a complex sugar molecule called glycogen, which the body’s cells — especially muscle cells — use as a source of energy.
In Pompe, due to a GAA deficiency or the lack of a functional GAA enzyme, glycogen builds up to toxic levels and causes damage to cells, particularly muscle cells.
As the name suggests, enzyme therapy for Pompe disease aims to “replace” the needed GAA enzyme. This is done by therapeutically administering a version of the enzyme that can get into the body’s cells and break down glycogen, thereby slowing or preventing the toxic glycogen buildup that drives Pompe disease symptoms.
It is generally recommended people with Pompe disease should start on ERT as early as possible. Once started, patients need to be on Pompe ERT for their entire lives in order to prevent toxic glycogen from building up again.
Available ERTs
There are two ERT products approved to treat Pompe disease in the U.S. Both treatments are sold by Sanofi and are administered intravenously, or via an infusion into the bloodstream, given every other week.
- Lumizyme (alglucosidase alfa) was the first ERT approved for Pompe disease; it became available in the U.S. in 2010. It is approved for all disease types in the U.S. and in a host of other countries, where it is marketed under the brand name Myozyme.
- Nexviazyme (avalglucosidase alfa) is a next-generation therapy designed to deliver the enzyme to muscle cells more efficiently than Lumizyme. It is approved in the U.S. for patients with late-onset Pompe disease ages 1 and older; it also is approved in other markets, though specific indications may differ.
| Brand name | Chemical name | Indication in the U.S. | Details |
|---|---|---|---|
| Lumizyme (Myozyme outside the U.S.) | Alglucosidase alfa | All types of Pompe disease | The first enzyme replacement therapy approved for Pompe disease |
| Nexviazyme | Avalglucosidase alfa | Late-onset Pompe disease in patients age 1 and older | A next-generation therapy designed to increase enzyme delivery to muscle cells |
ERT plus enzyme stabilizer
Pombiliti + Opfolda is a combination therapy approved in the U.S. for treating certain adults with late-onset Pompe disease who are not improving on their current ERT. It also is approved in other regions for adults with late-onset Pompe disease.
This two-part therapy consists of a lab-made version of the GAA enzyme, called cipaglucosidase (Pombiliti) and given via infusion, alongside an oral pharmacological chaperone called miglustat (Opfolda) that makes the enzyme more stable, helping maintain its activity.
Side effects
Treatments now available, whether ERT or the combination therapy Pombiliti + Opfolda, can cause allergic reactions, which may be severe in some patients. In those with underlying heart or breathing problems, these medications may cause a sudden drop in cardiac or respiratory function. Appropriate monitoring should be done during infusions.
Infusion-associated reactions, including nausea, fever, itching, rash, and coughing, may occur during or shortly after the administration of an ERT or Pombiliti. Such reactions are commonly managed by slowing or pausing the infusion and/or giving symptomatic treatment.
Serious and life-threatening infusion-associated reactions — including difficulty swallowing and trouble breathing — also have been reported.
Other side effects reported in clinical trials of ERT or Pombiliti + Opfolda include, but are not limited to:
- headache
- fatigue
- vomiting
- dizziness
- muscle pain
- hives or abnormal skin colorationshortness of breath
- increased blood pressure
- nausea
- abdominal pain
- fever.
The specific safety profile for ERT varies somewhat depending on the particular product used. Patients are advised to talk to their healthcare providers about any unexpected reactions to treatment.
Current ERT research
Numerous studies are ongoing into Pompe disease enzyme replacement therapy. They aim to learn more about the precise effects of available ERTs, find optimal ways to manage side effects and improve therapy administration, and increase the efficacy of these treatments.
One particular Phase 2 study (NCT04094948), run by Duke University, is testing clenbuterol — a therapy used in some countries to manage respiratory conditions, but not approved for human use in the U.S. This study seeks to determine if clenbuterol can improve motor function in adults with Pompe disease who are on a stable regimen of ERT.
Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about enzyme replacement therapy for Pompe disease
While other treatments may be administered to help manage the symptoms of Pompe disease, enzyme replacement therapies and the combination approach Pombiliti + Opfolda — which contains a version of the GAA enzyme alongside an enzyme stabilizer — are the only approved treatments that directly address the root cause of the disorder in order to slow disease progression.
There are two enzyme replacement therapies approved in the U.S.: Lumizyme and Nexviazyme. Lumizyme is approved for all forms of Pompe disease, while Nexviazyme is approved for patients with late-onset disease, ages 1 and older. Another approved therapy, Pombiliti + Opfolda, is a combination of a lab-made form of the GAA enzyme alongside an enzyme stabilizer. It is approved for certain adults with late-onset Pompe disease who are not improving on their current ERT.
Both approved enzyme replacement therapies, Lumizyme and Nexviazyme, are administered intravenously, or via an infusion into the bloodstream, every other week. Pombiliti, the lab-made form of the GAA enzyme given in a combination treatment with the enzyme stabilizer Opfolda, is also given every two weeks (Opfolda is taken about an hour before each Pombiliti infusion).
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