Skip to main content

A Different Approach to Enzyme Delivery1

POMBILITI + OPFOLDA is indicated for the treatment of adults with LOPD weighing ≥40 kg who are not improving on their current ERT2,3

IV bag-icon

POMBILITI is a naturally derived* bis-M6P–enriched enzyme2

  • Designed to be processed into the most active form of GAA2
  • Bis-M6P has ~3000x higher binding affinity to CI-MPR than M6P4
Capsule-icon

OPFOLDA is an enzyme stabilizer3

  • Binds with and stabilizes POMBILITI in the blood to increase the amount of active enzyme available to reach the muscle1-3
  • Reduces the inactivation of POMBILITI in the pH of the blood, which is unfavorable for rhGAA2,3,5,6

bis-M6P, bis-phosphorylated mannose 6-phosphate; CI-MPR, cation-independent mannose 6-phosphate receptor; ERT, enzyme replacement therapy; GAA, acid alpha-glucosidase; LOPD, late-onset Pompe disease; M6P, mannose 6-phosphate; rhGAA, recombinant human acid alpha-glucosidase.

*Enzyme derived from a Chinese Hamster Ovary (CHO) cell line using perfusion methodology, resulting in cellularly (CHO)-derived N-glycans.2

Mechanism of Action:

Designed to Maximize Enzyme Activity2

Developed to address key challenges in delivering rhGAA with a naturally derived* bis-M6P–enriched enzyme2,5†

Stability in the Blood1

1

OPFOLDA binds with and stabilizes POMBILITI in the blood and increases the amount of active enzyme that can reach the muscle1,3

Maximizing Uptake1

2

POMBILITI, a naturally derived* bis-M6P–enriched enzyme, in combination with OPFOLDA, binds with high affinity to CI-MPRs on the cell surface to be transported to the lysosome1,2

Complete Processing in the Lysosome2

3

Once inside the lysosome, OPFOLDA disassociates from POMBILITI3

4 5

POMBILITI is completely processed into the most active form of GAA, like endogenous GAA7-9

POMBILITI in its most active form cleaves glycogen into glucose2

*Enzyme derived from a Chinese Hamster Ovary (CHO) cell line using perfusion methodology, resulting in cellularly (CHO)-derived N-glycans.2

†Based on in vitro data.

Watch POMBILITI + OPFOLDA in action

Pharmacokinetics:

Adding OPFOLDA increased the availability of POMBILITI in the blood2

Pharmacokinetics of POMBILITI in the blood in ERT-experienced adults with LOPD

Mean AUC (±SD)10

Pharmacokinetics of POMBILITI digital illustration

 POMBILITI + OPFOLDA (n=10)‡§

 POMBILITI alone (n=11)‖¶

These pharmacokinetics data cannot be directly translated into clinical efficacy.

more POMBILITI was available in the blood with the addition of OPFOLDA2,10

Mean AUC0-inf (μg*hr/mL) (CV%)2#

Mean AUC values-digital illustration Mean AUC values-digital illustration

 POMBILITI + OPFOLDA (n=10)‡§

 POMBILITI alone (n=11)‖¶

AUC, area under the curve; CV, coefficient of variation.

†One subject was not dosed properly with OPFOLDA and was excluded from the analysis.10

‡POMBILITI 20 mg/kg + OPFOLDA 260 mg.2

§20 mg/kg.2

||POMBILITI is not approved for use without OPFOLDA.2

AUC0-inf is area under the curve (from time 0 to infinity), representing total drug exposure over time.2,11

References:

  1.  Schoser B, Roberts M, Byrne BJ, et al. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Lancet Neurol. 2021;20(12):1027-1037.
  2.  POMBILITI. Prescribing information. Amicus Therapeutics US, LLC; 2024.
  3.  OPFOLDA. Prescribing information. Amicus Therapeutics US, LLC; 2024.
  4.  Do HV, Khanna R, Gotschall R. Challenges in treating Pompe disease: an industry perspective. Ann Transl Med. 2019;7(13):291.
  5.  Johnson FK, Kang J, Mondick J, et al. Mechanism of action, plasma total GAA protein PK profiles and PK/PD relationships differ between cipaglucosidase alfa/miglustat and alglucosidase alfa in patients with late-onset Pompe disease. Poster presented at: The 18th Annual WORLDSymposium™; February 7-11, 2022; San Diego, CA, and virtually.
  6.  Thurberg BL, Maloney CL, Vaccaro C, et al. Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease. Lab Invest. 2006;86(12):1208-1220.
  7.  Selvan N, Mehta N, Venkateswaran S, et al. Endolysosomal N-glycan processing is critical to attain the most active form of the enzyme acid alpha-glucosidase. J Biol Chem. 2021;296:100769.
  8.  Selvan N, Venkateswaran S, Feng J, et al. Enhancing delivery of acid alpha-glucosidase (GAA) to skeletal muscle in Pompe disease (PD): key challenges and attributes of AT-GAA. Poster presented at: MDA Clinical & Scientific Conference; March 15-18, 2021; virtual.
  9.  Moreland RJ, Jin X, Zhang XK, et al. Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J Biol Chem. 2005;280(8):6780-6791.
  10.  Data on file, Amicus Therapeutics, Inc.
  11.  Ratain MJ, Plunkett WK Jr. Principles of pharmacokinetics. In: Kufe DW, Pollock RE, Weichselbaum RR, et al, eds. Holland-Frei Cancer Medicine. 6th ed. BC Decker; 2003. Accessed October 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK12815