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Walk a different path to treating LOPD

Choose the first and only two-component therapy in LOPD1,2

POMBILITI + OPFOLDA is indicated for the treatment of adults with LOPD weighing ≥40 kg who are not improving on their current ERT.1,2

POMBILITI™ (cipaglucosidase alfa‑atga) bis‑M6P enriched enzyme1,3,4

  • High CI-MPR binding affinity—for increased uptake into muscle cells
  • ~3000x the binding affinity of M6P
  • Can be processed into its most active form to break down glycogen
+

OPFOLDA™ (miglustat) oral stabilizer1‑3

  • Reduces inactivation of POMBILITI in the blood
  • Increases the amount of enzyme available for targeting skeletal muscle

bis-M6P, bis-mannose 6-phosphate; CI-MPR, cation-independent mannose 6-phosphate receptor; LOPD, late-onset Pompe disease; M6P, mannose 6-phosphate.

Mechanism of action

Developed to address key challenges in delivering rhGAA5*

1. Improving enzyme stability2,5

OPFOLDA stabilizes POMBILITI and increases the amount of active enzyme that is available for targeting to the muscle.

2. Enhancing enzyme uptake1,3

POMBILITI is enriched with the glycan bis-M6P, for higher binding affinity designed to improve uptake into the muscle.

3. Maximizing enzyme activity1

POMBILITI is processed to yield the most active form of GAA, and is designed to increase enzyme activity in the lysosome.

*Based on in vitro data.
rhGAA, recombinant human acid alpha-glucosidase.

Study design and baseline characteristics

PROPEL: A head-to-head, randomized, Phase III trial in predominantly ERT‑experienced adults1‑3

Nearly 80% of the study population was ERT-experienced

IV, intravenous; QOW, every other week.

  • Primary endpoint: Change from baseline to Week 52 in 6-minute walk distance (6MWD) for comparison of superiority§
  • Key secondary endpoint: Change from baseline to Week 52 in forced vital capacity (FVC)
  • Select inclusion criteria:
    • ≥18 years of age weighing ≥40 kg at screening
    • Confirmed diagnosis of LOPD
    • ERT-experienced adults were on either US-approved or non-US-approved alglucosidase alfa for ≥24 months
    • Sitting percent-predicted FVC of ≥30% of the predicted value for healthy adults
    • 6MWD of ≥75 meters at 2 screening tests
  • Key exclusion criteria:
    • Received previous treatment with any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days, or 5 half-lives of the therapy, before Day 1 of the study, whichever was longer
    • Received gene therapy for Pompe disease
    • Use of ventilation support for more than 6 hours per day while awake

*After database lock, 1 ERT-naïve subject was found to have intentionally underperformed at baseline. This subject was excluded from all 6MWD efficacy results; this change did not alter the statistical outcomes of the study.7
†POMBILITI in combination with OPFOLDA is not approved for use in ERT-naïve patients with LOPD. The ERT-naïve patient subgroup enrolled too few patients to conclusively interpret the data.1,3
‡Dosage based on patient weight.2
§Primary endpoint for superiority was not met.3

All ERT-experienced patients in the study had been treated for years3

Minimum treatment time for inclusion was 2 years

3+

OVER 90% of the ERT-experienced
cohort was treated for 3 OR MORE YEARS7

7.5

For the POMBILITI + OPFOLDA
group, the mean ERT
duration was 7.5 YEARS3

Select ERT-experienced baseline characteristics (ERT subgroup analysis: prespecified; n=95; 77%)3
BASELINE CHARACTERISTICS POMBILITI + OPFOLDA Comparator
ERT duration in years, mean 7.5 7.1
Age at first ERT dose in years, mean 40.8 38.7
Patients, n 65 30
6MWD, meters, mean 347 335
Sitting FVC, % predicted, mean 67.9 67.5

Results

ERT-experienced patients taking POMBILITI + OPFOLDA demonstrated measurable improvement in 6-minute walk distance (6MWD) and percent-predicted (PP) forced vital capacity (FVC) vs Comparator1,2*†

ERT-subgroup analysis: prespecified

Improvement in 6-minute walk distance1,2

Mean change from baseline (± SE) in 6MWD in ERT-experienced adults with LOPD1,2

*A US-approved alglucosidase alfa product was not used in this clinical trial. Conclusions cannot be drawn from this clinical trial regarding comparative effectiveness between a US-approved alglucosidase alfa product and POMBILITI in combination with OPFOLDA.1,2
†Primary endpoint for superiority was not met.3
‡For the ERT-experienced group, the treatment difference of the mean was estimated by nonparametric analysis of covariance that included treatment, gender, baseline 6MWD, age, weight, and height in the model. Missing data at Week 52 was imputed using last observed values.1,2

ERT-subgroup analysis: prespecified

Improvement in percent-predicted (PP) FVC1,2

Mean change from baseline (± SE) in % predicted FVC in ERT-experienced adults with LOPD1,2

*For the ERT-experienced group, the treatment difference of the mean was estimated by analysis of covariance that included treatment, gender, baseline FVC, age, weight, and height in the model. Missing data at Week 52 was imputed using last observed values.1,2

ERT-subgroup analysis: prespecified

Improvement in Hex4 biomarker1

In the ERT-experienced subgroup, POMBILITI + OPFOLDA showed a reduction in Hex4 (a metabolite of excess glycogen in patients with LOPD), as measured by Glc4 concentration. The Comparator showed an increase in Glc4.

Baseline Glc4 concentration:

  • POMBILITI + OPFOLDA: 4.6 mmol/mol
  • Comparator: 7.2 mmol/mol

CI, confidence interval; ERT, enzyme replacement therapy; GAA, acid alpha-glucosidase; Glc4, glucosidase tetrasaccharide; Hex4, hexose tetrasaccharide; IV, intravenous; SD, standard deviation; SE, standard error.

Demonstrated safety profile1,2

Safety profile was demonstrated across

151 PATIENTS in 3 CLINICAL TRIALS

  • The most common adverse reactions (≥5%) reported in the POMBILITI + OPFOLDA overall study population group of PROPEL were headache and diarrhea
  • The most common adverse reactions (≥5%) reported in the pooled safety population of patients treated with POMBILITI in combination with OPFOLDA in the 3 clinical trials were headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia
  • In these trials, serious adverse reactions reported in 2 or more patients treated with POMBILITI in combination with OPFOLDA were anaphylaxis and urticaria. A total of 5 patients treated with POMBILITI in combination with OPFOLDA in these trials permanently discontinued POMBILITI due to adverse reactions, including 4 of these patients who discontinued the treatment because of a serious adverse reaction
  • Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in POMBILITI-treated patients. In clinical trials, 41 (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)
  • In these trials, infusion-associated reactions were reported in 48 (32%) patients treated with POMBILITI in combination with OPFOLDA
  • There was no identified clinically significant effect of antidrug antibodies (ADA) on pharmacokinetics or pharmacodynamics of POMBILITI in combination with OPFOLDA over the treatment duration of 52 weeks. Because of the small number of patients with negative ADA, the effect of ADA on the effectiveness of POMBILITI in combination with OPFOLDA is unknown
Adverse reactions that occurred in adults with LOPD at an incidence of ≥2% in PROPEL1,2
Adverse Reactions POMBILITI + OPFOLDA
(n=85) N (%) 		Comparator
(n=38) N (%)
Headache* 7 (8.2) 3 (7.9)
Diarrhea 5 (5.9) 2 (5.3)
Dizziness 4 (4.7) 2 (5.3)
Dyspnea 3 (3.5) 0
Abdominal distention 3 (3.5) 2 (5.3)
Pyrexia 3 (3.5) 1 (2.6)
Rash† 3 (3.5) 0
Abdominal pain‡ 2 (2.4) 4 (10.5)
Nausea 2 (2.4) 5 (13.2)
Chills 2 (2.4) 0
Dysgeusia 2 (2.4) 0
Flushing 2 (2.4) 0
Muscle spasms 2 (2.4) 0
Pruritus 2 (2.4) 2 (5.3)
Tachycardia§ 2 (2.4) 0
Urticaria|| 2 (2.4) 0

*Headache included migraine and migraine with aura.
†Rash included erythematous rash and rash macular.
‡Abdominal pain included upper and lower abdominal pain.
§Tachycardia included sinus tachycardia.
||Urticaria included mechanical urticaria and urticarial rash.
ADA, antidrug antibodies.

Dosing, administration, and storage

Click or Tap to see additional Important Safety Information, including BOXED WARNING.

References:

  1.  POMBILITI. Prescribing information. Amicus Therapeutics US, LLC; 2023.
  2.  OPFOLDA. Prescribing information. Amicus Therapeutics US, LLC; 2023.
  3.  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.
  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.  Schoser B, Bratkovic D, Byrne B, et al. Long-term efficacy and safety of cipaglucosidase alfa/miglustat in ambulatory patients with Pompe disease: a Phase III open-label extension study (ATB200-07) (Data supplement). Poster presented at: 19th Annual WORLDSymposium™; Orlando, FL; February 22-26, 2023.
  7.  A study to assess the long-term safety and efficacy of ATB200/AT2221 in adult subjects with LOPD. ClinicalTrials.gov identifier: NCT04138277. Updated June 13, 2022. Accessed May 5, 2023. https://clinicaltrials.gov/ct2/show/NCT04138277