Pombiliti (cipaglucosidase alfa-agta) is an intravenous infusion that is given over approximately 4 hours by a healthcare provider in combination with oral Opfolda (miglustat) capsules (an enzyme stabilizer) for the treatment of adult patients with late-onset Pompe disease, who weigh at least 40kg (88 lb) and who are not improving on their current enzyme replacement therapy (ERT).

Pompe disease is a rare, inherited, debilitating, and life-threatening lysosomal disorder caused by a deficiency of the enzyme lysosomal acid alpha-glucosidase (GAA) that degrades glycogen to glucose. Reduced levels of GAA lead to the accumulation of glycogen in the lysosomes of muscle cells which causes muscle damage. Individuals with late-onset Pompe disease have lower levels of GAA, rather than no GAA. Symptoms can emerge at various stages of life, from infancy (although without heart enlargement, distinguishing it from infantile-onset Pompe disease) to childhood, adolescence, or even adulthood. This form of the disease tends to be less severe, primarily manifesting as muscle weakness that can eventually lead to breathing difficulties. Notably, late-onset Pompe disease typically does not affect the heart.

Without proper treatment, respiratory complications often become fatal for those affected by this condition. Pompe disease may also be called glycogen storage disease, type II, acid maltase deficiency, and glycogenosis type II).

Pombiliti is a hydrolytic lysosomal glycogen-specific enzyme that works by providing an exogenous source of GAA (cipaglucosidase alfa-agta). Pombiliti binds to receptors on the muscle cell surface and is then internalized and transported to lysosomes where it undergoes activation to GAA. It is then able to break down glycogen and reduce its concentration inside the cell.

Pombiliti was FDA approved on September 28, 2023.

Some people receiving Pombiliti have had serious allergic reactions during or shortly after infusion of this medicine. Tell your healthcare provider right away if you have any signs of a severe allergic reaction during the infusion, such as itching, rash, redness or tingling, severe headache, feeling light-headed, fast or slow heart rate, wheezing, trouble breathing, pale skin, and blue lips or fingernails. Pombiliti should be immediately discontinued if a severe infusion reaction occurs.

Before receiving Pombiliti, tell your doctor if you have heart disease, lung disease, or a breathing disorder, or if you have recently been sick with a cold, flu, or other illness. You may be at risk of a serious exacerbation of your heart or lung disease if you undergo a Pombiliti infusion.

Do not use it in pregnancy. May cause harm to an unborn baby. Females of reproductive potential should use effective contraception during treatment with Pombiliti and for at least 60 days after the last dose.

It is not known if Pombiliti is safe and effective in children.

There are risks associated with Opfolda as well. Please see here.

Pombiliti is administered at the same time as Opfolda.

Before the infusion, your healthcare provider may administer an antihistamine (such as diphenhydramine), an antipyretic (such as acetaminophen), and/or a corticosteroid to reduce the risk of an infusion reaction occurring.

• The recommended dosage is 20 mg/kg (actual body weight).
• Pombiliti infusion should be started approximately 1 hour after oral Opfolda. If it cannot be started within 3 hours, then it should be rescheduled in combination with Opfolda at least 24 hours later.
• Pombiliti is given as a slow infusion into a vein by a healthcare provider. The infusion usually takes approximately 4 hours; however, you will likely be in the clinic longer so there is time to administer your premedications, your dose of Opfolda, and for observation following the infusion.
• The dosage may need to be modified if hypersensitivity or infusion reactions occur.
• This medicine is usually given once every 2 weeks.

If you need surgery, tell the surgeon ahead of time that you are using Pombiliti.

To make sure Pombiliti is safe for you, tell your doctor if you have ever had:

• An allergic reaction to Pombiliti, cipaglucosidase alfa-agta, or any of the components of the injection
• Heart disease
• Lung disease or a breathing disorder
• A recent infection, such as a cold or a flu
• Are pregnant or plan to become pregnant
• Are breastfeeding.

Pombiliti may cause harm to an unborn baby. You may need to undergo a pregnancy test before you start treatment if you are of reproductive potential. Females of reproductive potential should use effective contraception during treatment with Pombiliti and for at least 60 days after the last dose. If you inadvertently become pregnant, tell your doctor right away.

You should not breastfeed while you are receiving Pombiliti. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

Pombiliti in combination with Opfolda may impair fertility in females and males.

Call your doctor for instructions if you miss an appointment for your Pombiliti injection.