Nexviazyme (avalglucosidase alfa) for Pompe disease
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What is Nexviazyme for Pompe disease?
Nexviazyme (avalglucosidase alfa) is an approved treatment for Pompe disease, developed by Sanofi, which has been shown to ease breathing and improve walking ability in people with the genetic disorder. It is marketed under the name Nexviadyme in Europe.
A next-generation enzyme replacement therapy (ERT), Nexviazyme provides patients with the enzyme missing in Pompe.
Therapy snapshot
| Brand name: | Nexviazyme |
| Chemical name: | Avalglucosidase alfa |
| Usage: | Enzyme replacement therapy used to ease breathing and improve walking ability |
| Administration: | Intravenous infusion |
How does Nexviazyme work?
Pompe disease is caused by mutations in the GAA gene, which provides instructions for making an enzyme called acid alpha-glucosidase. This enzyme is responsible for breaking down a complex sugar molecule called glycogen. In Pompe, decreased activity of the acid alpha-glucosidase enzyme results in the toxic accumulation of glycogen in body tissues, especially in muscle.
Nexviazyme contains a version of the acid alpha-glucosidase enzyme that can be administered therapeutically to “replace” the defective enzyme in people with Pompe disease. It was designed to deliver the enzyme to muscle cells and to lower glycogen levels more effectively than Lumizyme (alglucosidase alfa), an older enzyme replacement therapy also developed by Sanofi.
Who can take Nexviazyme?
In the U.S., Nexviazyme is approved to treat individuals with late-onset Pompe, ages 1 and older. It also is approved in Canada for the same disease type — late-onset, in which symptoms begin later in life — although it can be prescribed in that country to patients as young as 6 months. In Europe, the therapy is approved for late-onset and infantile-onset forms of Pompe.
The therapy also has been approved to treat forms of Pompe disease in Australia, Brazil, Japan, Switzerland, Taiwan, and the United Arab Emirates.
Who should not take Nexviazyme?
The U.S. prescribing information for Nexviazyme notes no contraindications. However, the therapy has boxed warnings regarding the risk of:
- severe hypersensitivity reactions, including anaphylaxis, which is a serious, life-threatening allergic reaction
- infusion-associated reactions
- acute cardiorespiratory failure in susceptible patients, such as those with an acute underlying respiratory disease or compromised cardiac or respiratory function.
How is Nexviazyme administered?
Nexviazyme is given via intravenous (into-the-vein) infusion every two weeks. The approved recommended dosage is:
- 20 mg/kg for patients who weigh at least 30 kg (about 66 pounds)
- 40 mg/kg for individuals who weigh less than 30 kg
The initial recommended infusion rate is 1 mg/kg per hour. This rate can be gradually increased in increments of 30 minutes if no infusion-related reactions occur. To reduce the risk of potential infusion-associated reactions, it is recommended patients be pretreated with anti-inflammatory medicines, such as antihistamines, antipyretics (fever-reducing medications), and/or corticosteroids.
Nexviazyme in clinical trials
An open-label Phase 1 clinical trial called NEO1 (NCT01898364) tested the safety and tolerability of Nexviazyme in 24 people with late-onset Pompe. Among them, 14 had previously used Lumizyme and the remaining 10 were new to ERT. All received the treatment for 24 weeks via infusions every other week.
Results from the NEO1 trial showed the treatment was generally safe and well-tolerated. Most side effects were mild to moderate in intensity, and there were no life-threatening adverse reactions or deaths during the study.
Infusion-associated reactions were reported in eight participants, and one participant withdrew from the study due to a serious side effect of chest discomfort and breathing difficulty.
Exploratory efficacy analyses suggested that lung and motor function generally was stable or improved for patients on Nexviazyme.
Participants who completed NEO1 had the option to enroll in an extension study called NEO-EXT (NCT02032524), which is still ongoing. It is collecting long-term data on the therapy, spanning up to six years.
An interim analysis of 17 patients treated for 5.5 years revealed no new safety concerns and indicated that lung and motor function were generally stabilized in these patients compared with what would be expected in untreated individuals with Pompe.
COMET study in late-onset Pompe
A Phase 3 clinical trial called COMET (NCT02782741) enrolled 100 patients with late-onset Pompe disease ages 3 and older who had never been on enzyme replacement therapy. Participants were randomly assigned to treatment with Nexviazyme or Lumizyme, each given at 20 mg/kg every other week, for 49 weeks.
The main goal of COMET was to assess the impact of treatment on forced vital capacity (FVC), a measure of lung function based on how much air a person can forcibly exhale in a breath.
Top-line results from COMET showed that FVC improvements with Nexviazyme were generally more pronounced than with Lumizyme, though the difference between the two therapies was not statistically significant. Nexviazyme also generally outperformed Lumizyme at increasing motor function, measured by the distance participants could walk in six minutes.
Participants who completed the initial COMET study had the option to enroll in an ongoing open-label extension study, in which all are being treated with Nexviazyme for 240 weeks (more than 4.5 years). Interim data suggested that the benefits of Nexviazyme seen in the initial study were maintained for up to two years.
Mini-COMET and Baby-COMET studies in infantile-onset Pompe
The Phase 2 Mini-COMET trial (NCT03019406) — designed for pediatric patients — enrolled 22 children with infantile-onset Pompe disease. The children, ages 6 months to 17 years, had previously failed to respond to Lumizyme.
Participants were randomly assigned to treatment with Nexviazyme at 20 or 40 mg/kg every other week or to continue on their current stable dose of Lumizyme. After about half a year, all participants were switched to Nexviazyme for the remainder of the study, which is expected to last up to seven years in total.
Six-month data showed that both doses of Nexviazyme were well-tolerated with no serious adverse events, deaths, or side effects leading to trial discontinuation. The early data also indicated that the next-generation ERT reduced levels of disease biomarkers, namely creatine kinase and hexose tetrasaccharide.
Two-year data from Mini-COMET showed no new safety-related findings, and none of the participants had signs of heart disease — a common complication of infantile-onset Pompe. Participants also showed stable or improved motor function after two years on Nexviazyme.
Another clinical trial called Baby-COMET (NCT04910776), now recruiting, aims to enroll 18 babies with infantile-onset Pompe, ages 12 months or younger. All participants will be treated with Nexviazyme, and the study’s main goal is to assess the proportion of participants who are alive and free of invasive ventilation after about one year. The study is enrolling participants at several locations in Europe and one in Asia.
Common side effects of Nexviazyme
The most common side effects of Nexviazyme include:
- headache
- fatigue
- diarrhea
- nausea
- joint pain
- dizziness
- muscle pain
- itching
- vomiting
- shortness of breath (dyspnea)
- reddening of the skin
- unusual tingling or pricking sensations (paresthesia)
- hives or welts (urticaria)
Allergic reactions
Nexviazyme carries a boxed warning for severe allergic reactions, including anaphylaxis. Appropriate supportive measures, including cardiopulmonary resuscitation (CPR) equipment, should be available when the treatment is administered. If a severe allergic reaction occurs, Nexviazyme should be immediately stopped, and appropriate care should be given.
Infusion-associated reactions
Patients may experience reactions during or shortly after infusions of Nexviazyme. These infusion-associated reactions are typically mild or moderate in severity and may be managed by slowing or pausing the infusion.
Severe reactions related to infusions — including chest discomfort, nausea, difficulty swallowing, trouble breathing, hives, tongue swelling, and increased blood pressure — have been reported in patients on Nexviazyme. If a severe reaction occurs, appropriate supportive care should be given, and discontinuing treatment should be considered. Patients and their healthcare teams should weigh the risk of future reactions against the potential benefits of treatment.
Risk of acute heart and/or lung failure in some patients
Individuals with underlying conditions that impair the heart and/or lungs, or those who are susceptible to fluid volume overload, may be at risk of serious worsening of heart/lung function following treatment with Nexviazyme. Appropriate vitals should be closely monitored in at-risk patients.
Pregnancy and breastfeeding
Nexviazyme has not been thoroughly studied in people who are pregnant or breastfeeding. Animal studies suggest that the therapy is not toxic to a developing fetus at clinically relevant doses, and available data for another enzyme replacement therapy (Lumizyme) have not shown an increased risk of adverse pregnancy outcomes.
The use of Nexviazyme during pregnancy or breastfeeding should be tailored based on the needs of the individual patient, taking into account the potential risks of untreated Pompe disease during pregnancy.
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 Nexviazyme
The U.S. Food and Drug Administration approved Nexviazyme in 2021 to treat late-onset Pompe disease in patients ages 1 and older.
Nexviazyme has not been well-studied in pregnant individuals. It is recommended that the therapy’s use during pregnancy be tailored based on the needs of the individual, in consultation with the patient’s healthcare team.
There is no direct evidence reported of an interaction between alcohol and Nexviazyme. Patients are, however, advised to talk to their healthcare providers about the use of alcohol or other substances while taking Nexviazyme.
Some patients have seen benefits in just over three months of treatment. In the COMET Phase 3 clinical trial that compared Nexviazyme against Lumizyme in people with late-onset Pompe disease, improvements in lung function with Nexviazyme were noted after about 13 weeks. There is, however, no standard timeline for Nexviazyme’s benefits, as each person may respond differently to the medication.
Neither hair loss nor weight gain has been reported as common side effects of Nexviazyme. People who experience unexpected effects after starting a new therapy are advised to seek the advice of their healthcare team.
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