General Information

Pombiliti (cipaglucosidase alfa-atga) is a recombinant human GAA enzyme. Opfolda (miglustat) is an enzyme stabilizer.

This two-component therapy is specifically indicated for adults living with late-onset Pompe disease (LOPD) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

Pombiliti is an intravenous infusion that is given over approximately 4 hours by a healthcare provider in combination with oral Opfolda (miglustat) 65mg capsules. 

• 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.
• The dosage may need to be modified if hypersensitivity or infusion reactions occur.
• This medicine is usually given once every 2 weeks.

Mechanism of Action

Pombiliti (cipaglucosidase alfa-atga) is a recombinant human GAA enzyme (rhGAA) naturally expressed with high levels of bis-M6P (Mannose 6-Phosphate), designed for increased uptake into muscle cells. Once in the cell, Pombiliti can be properly processed into its most active and mature form to break down glycogen. Opfolda (miglustat) is an enzyme stabilizer designed to stabilize the enzyme in the blood.

Side Effects

Adverse effects associated with the combination may include, but are not limited to, the following:

• headache
• diarrhea
• fatigue
• nausea
• abdominal pain
• pyrexia

Clinical Trial Results

FDA approval was based on data observed from the Phase 3 pivotal study (PROPEL) in LOPD ERT-experienced participants in a controlled setting. 

PROPEL was a 52-week, double-blind randomized global study designed to assess the efficacy, safety and tolerability of the combination (AT-GAA) compared to the current standard of care, alglucosidase alfa, an enzyme replacement therapy (ERT). The study enrolled 123 adult Pompe patients who still had the ability to walk and to breathe without mechanical ventilation and was conducted at 62 clinical sites in 24 countries on 5 continents. 

The primary endpoint of the study was the mean change in 6-minute walk distance as compared with baseline measurements at 52 weeks across the combined ERT switch and ERT naïve patient populations. In this combined population patients taking AT-GAA (n=85) walked on average 21 meters farther at 52 weeks compared to 7 meters with those treated with alglucosidase alfa (n=37).