Pompe Disease Respiratory Function Quick Points:

• Data from Pompe Registry
• 396 patients
• All on Enzyme Replacement Therapy (ERT)
• Examined upright FVC
• Median FVC (forced vital capacity) was 66.9%
  • FVC stable at 5 years -> Decline ~ 0.17%/yr
• Baseline FVC lower among some groups
  • Males
  • Older at ERT initiation
  • Longer duration from symptom onset to ERT initiation
  • More advanced disease
• Age of onset NOT associated with baseline degree of dysfunction
• Shorter time from diagnosis to ERT initiation associated with higher FVC after 5 years.
  • Cutoff of 1.7 years used in study
  • Neither short nor long groups’ declines were significantly different from 0.
    • Shorter-Time: − 0.07% predicted/year, p = 0.72;
    • Longer-Time: − 0.25% predicted/ year, p = 0.16

My take:

As a father of a newly diagnosed LOPD infant patient, this is a promising result. As I’m sure is the case with most of you reading, one of my greatest fears is that she (or you or your child) will deteriorate before more effective treatments can be found. The most fascinating finding was that respiratory function (measured with FVC) while on ERT was largely stable over five years. Similarly, although it is potentially better to have begun treatment within 1.7 years of diagnosis, even the group of patients that began ERT later than one year after diagnosis did not have a respiratory function decline significantly different than “no decline”.

With the improved treatments (hopefully) arriving in the not too distant future, a minimal degradation of FVC over five years is encouraging. With the two novel ERT treatments in phase 3 testing and now two current ongoing gene therapy trials [trial 1 and 2], there is certainly hope.

On the less positive side, Upright FVC is just one of many aspects of respiratory function. This result isn’t especially surprising, as most literature that I have read seems to suggest the same thing (while other performance measurements may experience more considerable declines). I guess it makes sense, however, as these patients were pulled from the Pompe Registry, it’s likely they were written about other previous studies.

Overall, this paper’s results is encouraging for those Pompe Disease to know that over five years it is likely that their upright breathing will not suffer significantly while on ERT.

Abstract

Objective

To examine respiratory muscle function among late-onset Pompe disease (LOPD) patients in the Pompe Registry (NCT00231400/Sanofi Genzyme) during enzyme replacement therapy (ERT) with alglucosidase alfa by assessing the longitudinal course of forced vital capacity (FVC), prognostic factors for FVC, and impact of time from diagnosis to ERT initiation.

Methods

Longitudinal FVC data from LOPD (symptom onset > 12 months or ≤ 12 months without cardiomyopathy) patients were analyzed. Patients had to have baseline FVC (percent predicted upright) assessments at ERT start and ≥ 2 valid post-baseline assessments. Longitudinal analyses used linear mixed-regression models.

Results

Among 396 eligible patients, median baseline FVC was 66.9% (range 9.3–126.0). FVC remained stable during the 5-year follow-up (slope = − 0.17%, p = 0.21). Baseline FVC was lower among various subgroups, including patients who were male; older at ERT initiation; had a longer duration from symptom onset to ERT initiation; and had more advanced disease at baseline (based on respiratory support use, inability to ambulate, ambulation device use). Age at symptom onset was not associated with baseline degree of respiratory dysfunction. Differences between subgroups observed at baseline remained during follow-up. Shorter time from diagnosis to ERT initiation was associated with higher FVC after 5 years in all patients and the above subgroups using a cut-off of 1.7 years.

Conclusion

FVC stability over 5 years suggests that respiratory function is preserved during long-term ERT in real-world settings. Early initiation of alglucosidase alfa was associated with preservation of FVC in LOPD patients with better respiratory function at the time of treatment initiation.

Mol Ther Methods Clin Dev. 2020 Sep 11; 18: 199–214. Published online 2020 Jun 10.
doi: 10.1016/j.omtm.2020.05.026

PMCID: PMC7334420

PMID:  32671132

Naresh Kumar Meena,¹Evelyn Ralston,²Nina Raben,^1,∗ and  Rosa Puertollano^1,∗∗

²Light Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA

¹Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA