Abstract
Aims
Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Second-generation ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation.
Materials and methods
A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and Phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6-minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, % predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and Network B, additionally including single-arm OLE and Phase I/II studies.
Results
Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93 m, 95% credible interval [8.26–50.11 m]; Bayesian probability 99.7%) and FVC (2.88 pp [1.07–4.71 pp]; >99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both endpoints. Analysis of Network A showed that cipa+mig was associated with a relative decrease in 6MWD (–10.02 m [–23.62–4.00 m]; 91.8%) and FVC (–1.45 pp [–3.01–0.07 pp]; 96.8%) compared with aval.
Conclusion
Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.
Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Second-generation ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation.
Materials and methods
A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and Phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6-minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, % predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and Network B, additionally including single-arm OLE and Phase I/II studies.
Results
Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93 m, 95% credible interval [8.26–50.11 m]; Bayesian probability 99.7%) and FVC (2.88 pp [1.07–4.71 pp]; >99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both endpoints. Analysis of Network A showed that cipa+mig was associated with a relative decrease in 6MWD (–10.02 m [–23.62–4.00 m]; 91.8%) and FVC (–1.45 pp [–3.01–0.07 pp]; 96.8%) compared with aval.
Conclusion
Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.
| Original language | English |
|---|---|
| Article number | e240045 |
| Number of pages | 15 |
| Journal | Journal of Comparative Effectiveness Research |
| Early online date | 17 Sept 2024 |
| DOIs | |
| Publication status | E-pub ahead of print - 17 Sept 2024 |
Research Groups and Themes
- HEHP@Bristol