Lumizyme (Alglucosidase Alfa) for Pompe Disease

Lumizyme (alglucosidase alfa) is an enzyme replacement therapy approved for Pompe disease. It works to ease breathing and improve motor function in patients with the genetic disorder.

The treatment was developed by Sanofi. Outside the U.S., it is marketed under the brand name Myozyme.

Therapy Snapshot

Pompe disease is an inherited condition caused by a genetic mutation that impairs the function of the enzyme acid alpha-glucosidase (GAA). This enzyme normally breaks down a complex sugar molecule called glycogen. As a result, glycogen builds up to toxic levels in body tissues, especially in muscle.

Excess glycogen impairs normal cellular functions and causes cell death, resulting in muscle weakness and loss of respiratory function. It can potentially lead to heart failure.

An enzyme replacement treatment, Lumizyme contains a functional version of the GAA enzyme that can be delivered to cells, thereby facilitating glycogen clearance. Thus, the therapy can reduce the severity of Pompe disease symptoms experienced by patients.

In the U.S., Lumizyme is approved to treat all types of Pompe disease. The therapy also is approved for this indication in other markets, including in the EU and Canada, where it is marketed as Myozyme.

The U.S. prescribing information for Lumizyme lists no contraindications. However, the therapy has boxed warnings noting the risk of:

• allergic and anaphylactic reactions, which may be life-threatening
• worsening of heart or lung function in children with infantile-onset Pompe who have pre-existing cardiac or respiratory problems.

Lumizyme is given via an intravenous (into-the-vein) infusion every two weeks. The approved dosage is 20 milligrams per kilogram of body weight (mg/kg).

The initial infusion rate should be no faster than 1 mg/kg/hour; it may be gradually increased up to a maximum of 7 mg/kg/hour based on the patient’s tolerance to the infusion rate.

The infusion rate may be slowed or paused if patients experience any mild to moderate allergic reactions. If a severe reaction occurs, the infusion should be discontinued.

The initial approval of Lumizyme in the U.S. was supported by data from a Phase 3 clinical trial (NCT00158600) completed in 2007. It enrolled 90 ambulatory people ages 8 and older with late-onset Pompe disease. Some patients required assistive walking devices.

Participants were randomly assigned to infusions of Lumizyme (20 mg/kg) or a placebo, given every other week for 78 weeks. A total of 81 patients completed the trial.

The study’s main goals were to assess the treatment’s impact on the distance participants could walk in six minutes — a common measure of motor function — as well as forced vital capacity (FVC), a test of lung function based on how much air someone can forcibly exhale in one breath.

Results showed that, in the patients on Lumizyme, six-minute walk distances increased by an average of 25.1 meters (about 82 feet). Meanwhile, the walked distance decreased by an average of 3 meters (about 10 feet) in patients on the placebo.

Similarly, average FVC increased by 1.2 percentage points for patients on Lumizyme, whereas it decreased by 2.2 percentage points for those given the placebo.

Trials in infantile-onset disease

Three clinical trials provided the basis for Lumizyme’s approval to treat infantile-onset Pompe disease in the U.S.

One Phase 2/3 study (NCT00059280) enrolled 18 babies, ages 7 months or younger, who showed clinical signs of Pompe disease with heart involvement. Patients were treated with Lumizyme at 20 or 40 mg/kg every other week for at least one year.

By 18 months of age, 15 of the children (83%) were alive and free of ventilator support, the results showed. The other three children were alive and required invasive ventilator support.

These findings markedly contrasted with the typical course of infantile-onset disease without treatment. No differences were seen between the two dosing regimens tested.

Another Phase 1/2 trial (NCT00053573) enrolled 21 children, ranging in age from 3 months to 3.5 years. Five of these children were on ventilator support when they started treatment. All participants received Lumizyme at 20 mg/kg every other week for a median of 120 weeks.

At the end of study, 15 of the 21 participants were alive — causes of death were cardiac and/or respiratory failure in all cases — and of the 16 who had been off ventilation at the study’s start, seven still did not need ventilatory support. Improvements in motor function also were reported in some patients. Again, these findings markedly differed from what would be expected in untreated infantile-onset Pompe.

The third study enrolled 18 babies with Pompe disease who were identified via a newborn screening program, and who started on Lumizyme treatment within the first few months of life (prior to 6 months of age). At age 18 months, all evaluable patients (16 in total) were alive without a need for ventilation. 

Ongoing trials

Sanofi is sponsoring several trials to continue gathering data on Lumizyme. A one-year Phase 4 study called APOLLO-LOPD (NCT04676373) is testing the therapy’s effects on motor and lung function in Chinese patients with late-onset disease, ages 3 and older.

Another study (NCT04848779), being conducted in Europe and Taiwan, is tracking ventilation-free survival outcomes for babies with infantile-onset disease who start on Lumizyme before age 6 months.

Lumizyme’s safety and tolerability in an at-home-care infusion setting are being assessed in a study taking place in Italy, called HomERT (NCT05073783).

The most common side effects of Lumizyme reported in clinical trials were:

• anaphylaxis (a severe allergic reaction)
• rash
• fever
• flushing or feeling hot
• hives or welts (urticaria)
• headache
• excessive sweating
• nausea
• cough
• decreased amounts of oxygen in the blood
• abnormally fast heart rate and/or breathing
• chest discomfort
• dizziness
• muscle twitching
• agitation
• skin turning bluish or red (cyanosis)
• redness of the skin (erythema)
• increased blood pressure
• pallor
• rigors (sudden bouts of cold shivering)
• tremor
• vomiting
• fatigue
• muscle pain

Allergic reactions

Lumizyme carries a boxed warning for severe allergic reactions, including anaphylaxis, which can occur during or after infusions of Lumizyme. Patients should be closely monitored for signs and symptoms of allergic reactions, and the treating clinicians should be prepared to administer appropriate treatment if a reaction occurs.

Risk of worsening heart and/or lung issues in some patients

Patients with Pompe disease who have compromised cardiac or respiratory function may be at risk of a sudden worsening of heart/lung status following treatment with Lumizyme. Thus, these patients require additional monitoring.

Caution also should be used when administering general anesthesia for the placement of a central venous catheter for Lumizyme infusion, as an irregular heartbeat, resulting in cardiac arrest or death, has been observed in infantile-onset Pompe disease patients with compromised cardiac function.

Risk of antibody development

Patients with infantile-onset Pompe disease should undergo a cross-reactive immunologic material (CRIM) assessment early on, as the CRIM status can influence the patients’ response to treatment. Clinical specialists in immune tolerance induction in Pompe disease should be involved to optimize treatment.

Pregnancy and breastfeeding

Data from post-marketing and case reports have shown no association between the use of Lumizyme and any complications related to pregnancy, including major birth defects, miscarriage, or adverse maternal or fetal outcomes.

The medication’s use in pregnancy should be tailored to the individual, taking into account that untreated Pompe disease may result in worsening symptoms during pregnancy. Individuals on Lumizyme who are or may become pregnant are encouraged to enroll in the Pompe patient registry.

Lumizyme is present in human breastmilk, but there are no reports of adverse effects on breastfed infants. Patients who are breastfeeding while on Lumizyme may consider interrupting breastfeeding, or pumping and discarding breast milk around the time they receive infusions, to reduce exposure to the nursing baby.