Enzyme replacement therapy for Pompe disease
Last updated Nov. 1, 2024, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD
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?
As the name suggests, enzyme therapy for Pompe disease aims to “replace” 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 skeletal muscle cells — use as a source of energy. In Pompe, due to mutations in the gene that codes for GAA, there is a lack or insufficient levels of functional enzyme, leading to glycogen buildup to toxic levels and causing damage to cells.
ERT works 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 that people diagnosed with Pompe disease should start on ERT as early as possible. Once started, patients need to be on Pompe ERT for their entire lives.
Available ERTs
Two ERT medications are approved for Pompe disease in the U.S. Both 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, and 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.
| 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, 1 year 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 certain adults with late-onset Pompe disease who are not improving on their current ERT. It is also 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), given via infusion, alongside an oral pharmacological chaperone called miglustat (Opfolda) that makes the enzyme more stable, helping maintain its activity.
Learn more about Pombiliti + Opfolda here.
Side effects
Pompe disease 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, have also 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 coloration
- shortness 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 the safety and efficacy of Pompe disease ERT. Whether the treatment burden for patients can be eased is also being evaluated.
Amicus Therapeutics, the developer of Pombiliti + Opfolda, is currently sponsoring a global, observational registry trial (NCT06121011) to explore the long-term safety and efficacy of Lumizyme, Nexviazyme, and Pombiliti + Opfolda in real-world practice. The study also seeks to assess the natural progression of Pompe disease in untreated participants. Both infantile-onset and late-onset patients may be eligible.
In participants with infantile-onset Pompe disease, a natural history study (NCT01665326) at Duke University Medical Center is exploring response to Lumizyme and how it is affected by CRIM (cross-reactive immunological material) status, which is a measure of natural GAA activity that impacts ERT response. The trial seeks to analyze response to immunosuppressive therapy in patients deemed at risk for developing, or who have developed, high and sustained antibodies against ERT, which may render treatment ineffective.
Another trial, a Phase 4 study called TRIPOD (NCT06575829), sponsored by Erasmus Medical Center in the Netherlands, will evaluate whether reducing the dosing frequency of Lumizyme (20 mg/kg) from once every two weeks to once every four weeks is safe and is as effective in slowing disease progression in people with late-onset Pompe disease. Patients 50 or older may be eligible to participate.
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.
Two enzyme replacement therapies are approved in the U.S.: Lumizyme and Nexviazyme. Lumizyme is approved for all forms of Pompe disease, while Nexviazyme is approved for patients, 1 year and older, with late-onset disease. 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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