Cipaglucosidase Alfa

Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is an inherited disorder of glycogen metabolism caused by a deficiency of lysosomal acid alpha‑glucosidase (GAA) that degrades glycogen to glucose in the lysosome. GAA deficiency results in intra-lysosomal accumulation of glycogen in various tissues.

• POMBILITI is indicated, in combination with Opfolda, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT). POMBILITI is a hydrolytic lysosomal glycogen-specific enzyme indicated, in combination with Opfolda, an enzyme stabilizer, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

• POMBILITI in combination with Opfolda is contraindicated in pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ].contraindicated

Verify pregnancy status in females of reproductive potential prior to initiating treatment. ( 2.1 ) Administer POMBILITI in combination with Opfolda. ( 2.2 ) Consider administering antihistamines, antipyretics, and/or corticosteroids prior to POMBILITI administration. ( 2.2 ) Recommended POMBILITI dosage is 20 mg/kg (of actual body weight) administered every other week as an intravenous infusion over approximately 4 hours. ( 2.2 ) Start POMBILITI in combination with Opfolda 2 weeks after the last ERT dose. ( 2.2 ) Initiate the POMBILITI infusion approximately 1 hour after oral administration of Opfolda. If the POMBILITI infusion cannot be started within 3 hours of oral administration of Opfolda, reschedule POMBILITI in combination with Opfolda at least 24 hours after Opfolda was last taken. If POMBILITI in combination with Opfolda are both missed, re-start treatment as soon as possible. ( 2.2 ) See the full prescribing information for dosage modifications due to hypersensitivity reactions or IARs. ( 2.3 ) Must be reconstituted and diluted prior to use. ( 2.4 ) See the full prescribing information for administration instructions. ( 2.6 ) 2.1 Pregnancy Evaluation Prior to Initiating Treatment Verify the pregnancy status of females of reproductive potential prior to initiating POMBILITI in combination with Opfolda [see Use in Specific Populations (8.1 , 8.3 )] . 2.2 Recommended Dosage and Administration POMBILITI must be administered in combination with Opfolda (see Figure 1 for the dosing timeline). If the Opfolda dose is missed, POMBILITI should not be administered.

Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose. ( 4 , 5.4 , 8.1 , 8.3 ) Risks Associated with Opfolda: Refer to the Opfolda Prescribing Information for a description of additional risks for Opfolda. ( 5.5 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in POMBILITI-treated patients. In clinical trials, 43 (27%) POMBILITI-treated patients experienced hypersensitivity reactions, including 4 (3%) patients who reported severe hypersensitivity reactions and 4 (3%) additional patients who experienced anaphylaxis (fulfilling at least one of the Sampson criteria). Three of the 4 (2%) patients experiencing anaphylaxis discontinued from the trial [see Clinical Studies (14) ] . Two of the 4 patients who experienced anaphylaxis developed high anti-cipaglucosidase alfa-atga antibody titers [see Clinical Pharmacology (12.6) ] . Anaphylaxis signs and symptoms included dyspnea, rash, hypotension, bronchospasm, edema, pharyngeal edema, and tongue swelling. Symptoms of severe hypersensitivity reactions included urticaria, pruritus, and flushing. Prior to POMBILITI administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during POMBILITI administration.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion-Associated Reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions ≥ 5% are headache, diarrhea, fatigue, nausea, abdominal pain and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amicus Therapeutics at 1-877-4AMICUS or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from the Pooled Clinical Trials Including Trial 1 The pooled safety analysis from 3 clinical trials included 151 adult patients with late-onset Pompe disease (LOPD) treated with POMBILITI in combination with Opfolda including: 85 patients in the randomized, double-blind, active-controlled trial in adults (Trial 1) [see Clinical Studies (14) ] , 37 patients in the open-label extension trial where patients switched from a non‑U.S.‑approved alglucosidase alfa product [see Clinical Studies (14) ] to POMBILITI in combination with Opfolda, 29 patients in an open-label trial. The total median duration of exposure in these trials was 21 months, with 120 patients having at least 12 months exposure to POMBILITI in combination with Opfolda.

Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, POMBILITI in combination with Opfolda may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy. In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with cipaglucosidase alfa-atga in combination with miglustat at 16-fold and 3-fold, respectively, the MRHD of POMBILITI and Opfolda based on plasma AUC exposure. A No Observed Adverse Effect Level (NOAEL) was not identified for the combination. In a pre- and post-natal development study in rats, increases in pup mortality were seen following maternal treatment with cipaglucosidase alfa-atga (400 mg/kg) in combination with miglustat, or with cipaglucosidase alfa-atga (400 mg/kg) alone. The NOAEL for cipaglucosidase alfa-atga alone is 150 mg/kg (5-fold the POMBILITI MRHD margin). A NOAEL for the combination was not identified. Margins at the lowest observed adverse effect level (LOAEL), relative to exposures at the MRHD of POMBILITI and Opfolda were 20-fold and 4-fold, respectively, based on plasma AUC exposure (see Data ) .

Metabolism

The maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of cipaglucosidase alfa-atga following administration with 20 mg/kg of cipaglucosidase alfa-atga in combination with a single oral dose of 260 mg of Opfolda in adult patients with LOPD are summarized in Table 3 . Table 3.

• Sep 28, 2023BLABLA761204Amicus Therap Us

1. 1Death58.1%
2. 2Fatigue58.1%
3. 3Pneumonia58.1%
4. 4Product Dose Omission Issue58.1%
5. 5Dyspnoea46.5%
6. 6Malaise46.5%
7. 7Motor Dysfunction46.5%
8. 8Abdominal Pain Upper34.8%
9. 9Gastritis34.8%
10. 10Hypertension34.8%
11. 11Intentional Dose Omission34.8%
12. 12Nausea34.8%
13. 13Off Label Use34.8%
14. 14Product Availability Issue34.8%
15. 15Pruritus34.8%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Cipaglucosidase Alfa as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Global Prospective Observational Registry of Patients With Pompe Disease
  Recruiting · Observational · 500 enrolled · Amicus Therapeutics
  NCT06121011updated 2026-03-10
• A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD)
  Completed · Phase 3 · Interventional · 119 enrolled · Amicus Therapeutics
  NCT04138277updated 2026-03-05
• A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
  Recruiting · Phase 3 · Interventional · 36 enrolled · Amicus Therapeutics
  NCT04808505updated 2026-01-22
• ZIP Study-OL Study of Safety, PK, Efficacy, PD, Immunogenicity of ATB200/AT2221 in Pediatrics Aged 0 to < 18 y.o. w/LOPD
  Active not recruiting · Phase 3 · Interventional · 21 enrolled · Amicus Therapeutics
  NCT03911505updated 2025-10-27
• First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
  Completed · Phase 1 · Phase 2 · Interventional · 29 enrolled · Amicus Therapeutics
  NCT02675465updated 2025-10-23
• A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease
  Completed · Phase 3 · Interventional · 125 enrolled · Amicus Therapeutics
  NCT03729362updated 2025-09-11

Frequently asked questions

How does Cipaglucosidase Alfa work?

Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is an inherited disorder of glycogen metabolism caused by a deficiency of lysosomal acid alpha‑glucosidase (GAA) that degrades glycogen to glucose in the lysosome. GAA deficiency results in intra-lysosomal accumulation of glycogen in various tissues.

What is Cipaglucosidase Alfa used for?

According to FDA labeling, Cipaglucosidase Alfa carries indications including: POMBILITI is indicated, in combination with Opfolda, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT). POMBILITI is a hydrolytic lysosomal glycogen-specific enzyme indicated, in combination with Opfolda, an enzyme stabilizer, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Cipaglucosidase Alfa?

Cipaglucosidase Alfa is classified as Enzymes, Enzymatic Activity, Increased Lysosomal Function.

What are the brand names for Cipaglucosidase Alfa?

Cipaglucosidase Alfa is marketed under brand names including Pombiliti.

What are the contraindications for Cipaglucosidase Alfa?

Cipaglucosidase Alfa labeling lists contraindications including: POMBILITI in combination with Opfolda is contraindicated in pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ].. Always consult the full prescribing information and a clinician.