Managing Late-Onset Pompe Disease With Pombiliti

Written by Bonnie Bachenheimer, PharmD, BCPS
Medically Reviewed by Beth Johnston, PharmD, BCPS on September 10, 2025
7 min read

Pombiliti (cipaglucosidase alfa-atga) is a medicine taken with another medicine for certain people with late-onset Pompe disease. Pompe disease is a rare genetic disorder that is caused by an abnormal gene for a protein (enzyme) called acid alpha-glucosidase (GAA). GAA breaks down glycogen into glucose, a form of sugar stored in muscles and other tissues. In people with Pompe disease, there is not enough GAA, so glycogen builds up in muscle cells. This causes muscle weakness and other symptoms that get worse over time.

There are three different types of Pompe disease based on when symptoms first appear. Each type has slightly different symptoms, shows up at different ages, and varies in how serious it is. In some people, the GAA enzyme does not work at all, and in others, it still works to some extent. 

  • Classic infantile-onset disease shows up within the first three months after birth and is the most serious form.  
  • Non-classic infantile-onset disease is usually less severe than the classic form and shows up during the first year of life. The main symptoms of infantile-onset disease are weak muscles, poor muscle tone, and an abnormally large heart. 
  • Late-onset Pompe disease may show up during late childhood, the teenage years, or in adults. It is usually milder than infantile-onset disease and is less likely to involve the heart. Symptoms include muscle weakness, especially in the torso and legs, and in the diaphragm, which leads to breathing problems. 

The main treatment for all types of Pompe disease is enzyme replacement therapy (ERT). Recombinant human acid alpha-glucosidase (Lumizyme) and avalglucosidase alfa-ngpt (Nexviazyme) are examples of ERT. Treatment is given into your vein (IV) and helps reduce the amount of glycogen in your muscles. 

Other supportive therapies include physical therapy, occupational therapy, and speech therapy. People with Pompe disease may need to use canes, walkers, or wheelchairs to help with mobility and ventilators for breathing support.

Pombiliti is a medicine approved to be used with another medicine called Opfolda (miglustat) for certain people with late-onset Pompe disease who weigh 88 pounds or more and are not improving on their current ERT.

The main ingredient in Pombiliti is cipaglucosidase alfa-atga, a medicine that provides the enzyme that breaks down glycogen. It is always given with Opfolda. Opfolda binds to and stabilizes Pombiliti in your blood so more Pombiliti can get into your muscle cells. After Pombiliti is in the cells, Opfolda separates from Pombiliti. Pombiliti begins working to break down glycogen and change it into glucose. This helps lower the amount of glycogen in muscles.

Pombiliti is given as an intravenous (IV) infusion through a needle placed in your vein by a health care provider in a hospital or clinic. The infusion is given once every two weeks. Each infusion lasts about four hours. 

Pombiliti is always given with Opfolda. Opfolda is a capsule that is taken by mouth on an empty stomach about one hour before your Pombiliti infusion starts. If you miss your Opfolda dose, you will not be able to receive Pombiliti.

Pombiliti can cause IV-related reactions and allergic reactions, so your health care provider will monitor you for these side effects during and after your infusion. Your health care provider may slow or stop your infusion if you have a reaction. If you have side effects from the infusion or if you have had reactions with other ERT, you may be given medicines — such as acetaminophen, diphenhydramine (or another antihistamine), , and/or hydrocortisone (or another steroid) — by mouth or IV about 30 minutes before your Pombiliti infusion to prevent or lessen side effects.

The effectiveness and safety of Pombiliti plus Opfolda in adults with late-onset Pompe disease was studied in a clinical trial called PROPEL.

Here are some details about the people in the study.

  • All the people in the study were 18 years of age or older with a weight of 88 pounds or more and had late-onset Pompe disease based on documentation of GAA enzyme deficiency or gene studies.
  • People had either been taking an ERT called alglucosidase alfa every two weeks for at least two years (ERT-experienced) or had not received any treatment with ERT (ERT-naive).
  • The study included a total of 123 people, and the average age was 47 (range, 19-74) years. 
    • Most of the people in the study were female (54%), and the rest were male.
    • Most were White (85%), 8% were Asian, 1% were Black or African American, 1% Native Hawaiian or other Pacific Islander, 1% Native American or Alaska Native, and 5% identified their race as Other.
    • Most people (77%) were ERT-experienced, and the average length of treatment with alglucosidase alfa before the study was 7.4 years.

People in the study were treated with an IV infusion of Pombiliti plus Opfolda or an IV infusion of alglucosidase alfa plus a placebo (containing no medicine) every two weeks for 52 weeks.  There were 85 people in the Pombiliti plus Opfolda group and 38 people in the alglucosidase alfa plus placebo group. The alglucosidase alfa medicine used in the study is not an approved medicine in the U.S.

The main goal of the study was to see how much farther people who received Pombiliti plus Opfolda could walk in six minutes using a test called the 6-minute walk distance (6MWD). This was measured on a flat surface with walking shoes. Walking aids such as a cane or walker were allowed.

Another goal of the study was to measure the change from baseline to week 52 in breathing ability between groups using a test called the sitting forced vital capacity (FVC). The FVC is the largest amount of air you can exhale forcefully after taking in as big a breath as you can. An FVC percent predicted (FVC%) compares your FVC result to the average or normal predicted value for someone the same age, sex, and height as you. An FVC% of 80% or higher is a typical normal lung volume.

After one year, the change from baseline in the Pombiliti plus Opfolda group for the 6MWD was about 21 meters, and the change from baseline in the alglucosidase alfa plus placebo group was about 7 meters. The estimated treatment difference between the groups was 14 meters.

The people that were ERT-experienced who were treated with Pombiliti plus Opfolda had a positive change in their walking distance after one year. There were not enough people in the ERT-naive group to be able to interpret the results for walking distance. More studies are needed to see if there are differences between these groups.

People that were ERT-experienced who were treated with Pombiliti plus Opfolda had stable or small improvements in their breathing ability as measured using the FVC. After one year, the average change from baseline in the Pombiliti plus Opfolda group was -1.1%, and the change from baseline in the alglucosidase alfa plus placebo group was -3.3%. The estimated treatment difference between the groups was 2.3%. There were not enough people in the ERT-naive group to be able to interpret this information. At this time, Pombiliti is only approved for people who are ERT-experienced.

People who were treated with Pombiliti plus Opfolda had lower levels of Hex4 biomarkers, which is a sign that there were lower levels of glycogen in the blood.

Your results may differ from what was seen in clinical studies. 

Serious side effects that may happen when you get your Pombiliti infusion include the following.

Allergic reactions (hypersensitivity reactions). You may have allergic reactions to Pombiliti that may be serious. These include shortness of breath, trouble breathing, rash, a drop in your blood pressure, swelling of your throat or tongue, itching, hives, or redness.

Infusion reactions. You may have reactions during or within a few hours after your Pombiliti infusion. This may happen even if you receive medicines to prevent reactions before the infusion. Most reactions related to the infusion are mild, but some may be serious. These include throat swelling, anaphylaxis, hives, itching, chills, shortness of breath, flushing, and a drop in blood pressure.

Heart or lung (cardiorespiratory) failure. Some people with heart or lung problems may have serious worsening of their disease during the infusion. Your health care provider may need to check on you more often during the infusion and for a longer period of time after the infusion if you have:

Tell your health care provider right away if you have any symptoms of an allergic reaction or infusion reaction.

There is a patient support program offered by the drugmaker called Amicus Assist that may help you afford Pombiliti. Your health care provider can help you get started. You can find out more at pombilitiopfolda.com/support-and-tools or by calling 833-AMICUS-A (833-264-2872).