Opfolda (miglustat) is an enzyme stabilizer medicine used in the treatment of late-onset Pompe disease in adults. Opfolda capsules are used in combination with Pombiliti (cipaglucosidase alfa-atga) infusion. The Opfolda capsules are taken to increase the effectiveness of Pombiliti. Opfolda binds to Pombiliti to stabilize and protect it in the bloodstream after infusion. Then once it has been absorbed into the cells Pombiliti becomes unbound so that it can break down excessive glycogen.

Late-onset Pompe disease is a inherited, rare, debilitating, and life-threatening disease caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). Low levels of GAA cause a build up of glycogen in muscle cells which causes muscle damage. Symptoms of late-onset Pompe disease are caused by progressive muscle weakness and include leg and torso weakness, breathing difficulties, sleep apnea, difficulty eating, digestive problems and enlarged heart. Pompe disease may also be called glycogen storage disease, type II, acid maltase deficiency, and glycogenosis type II.

How do Opfolda + Pombiliti work for Pompe disease?

Pombiliti (cipaglucosidase alfa-agta) is a hydrolytic lysosomal glycogen-specific enzyme. Pombiliti works by being a replacement for the missing enzyme acid alpha-glucosidase (cipaglucosidase alfa-agta). When Pombiliti is absorbed into the muscle cells it gets converted to GAA so it is then able to break down glycogen which reduces glycogen toxic levels.

If Pombiliti is administered without Opfolda, it becomes inactive in the bloodstream after infusion, making it less effective. However, when Pombiliti and Opfolda are used together, Opfolda helps keep Pombiliti stable and protected in the bloodstream, making Pombiliti more effective.

Is Opfolda and Pombiliti FDA-approved?

Yes, Opfolda and Pombiliti became FDA-approved medicines on September 28, 2023, they are separate FDA-approved medicines that are used together for the treatment of late-onset Pompe disease. Opfolda + Pombiliti is called a two-component therapy. 

Who can use Opfolda?

Opfolda can be used for adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) who weigh 40kg or more and are not improving on their current enzyme replacement therapy (ERT). Opfolda is an enzyme stabilizer and is used in combination with Pombiliti, a hydrolytic lysosomal glycogen-specific enzyme.

Do not take Opfolda in combination with Pombiliti if you are pregnant. 

Opfolda must be administered in combination with Pombiliti.
Refer to the Pombiliti Prescribing Information for a description of additional risks for Pombiliti including, but not limited to, the warnings and precautions for Pombiliti. 

Opfolda is a capsule that is taken combination with Pombiliti infusion. 

Opfolda +  Pombiliti  treatment is one time every other week.

Take your prescribed dose of Opfolda about 1 hour before the start of your Pombiliti infusion.

Opfolda capsules should be swallowed whole only with unsweetened beverages, including water, tea or coffee, with no cream, sugar, or sweeteners. Do not drink other beverages or eat food for at least 2 hours before and 2 hours after taking the capsule.

Your current enzyme replacement therapy (ERT) will be stopped 2 weeks before starting your treatment with Opfolda + Pombiliti.

If you miss taking your Opfolda dose, you should not receive your Pombiliti infusion. Call your healthcare provider right away to reschedule your Pombiliti infusion. 

Recommended Adult Opfolda dosage 

Dose is based on actual body weight and administered orally every other week.

Dose:

• 260 mg for patients weighing ≥50 kg.
• 195 mg for patients weighing ≥40 kg to <50 kg. 

Comment: See full prescribing information for recommended dosage in patients with renal impairment.

Opfolda + Pombiliti should be used together.

Before taking Opfolda, tell your healthcare provider about all of your medical conditions, including if you:

•   have any kidney problems  

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant. Opfolda when taken in combination with Pombiliti may cause harm to your unborn baby. 

Females who are able to become pregnant: 

• You should have a pregnancy test to ensure you are not pregnant before you start treatment with Opfolda + Pombiliti. 
• You should use effective birth control (contraception) during treatment with Opfolda + Pombiliti, and for at least 60 days after the last dose. 
• If you become pregnant or think you might be pregnant during treatment with Opfolda in combination with Pombiliti you should tell your healthcare provider right away. 

Infertility

Advise the male or female of reproductive potential that taking Opfolda with Pombiliti may cause fertility problems, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility. 

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Opfolda alone or in combination with Pombiliti will pass into your breast milk. Do not breastfeed during treatment with Opfolda in combination with Pombiliti. Talk to your healthcare provider about the best way to feed your baby during this time. 

Common Opfolda side effects

The most common side effects affecting 5% or more of patients using Opfolda + Pombiliti in the 3 clinical trials were headache, diarrhea, fatigue, nausea, abdominal pain, and fever.

Less common Opfolda side effects 

Other side effects that affected at least 2% of patients treated with Opfolda in combination with Pombiliti across the 3 clinical trials include: muscle pain, joint pain, increased blood pressure, pain, tremor, indigestion, weakness or lack of energy, constipation, infusion site swelling, flank pain, malaise, decreased platelet count, and a burning prickling sensation in parts of the body. 

These are not all of the possible side effects of Opfolda in combination with Pombiliti. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. 

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.