Amicus Therapeutics recently announced topline results of its phase 3 PROPEL study of its combination therapy, AT-GAA, for the treatment of late onset Pompe disease (LOPD). While the results were good, they were not great. More specifically, the primary endpoint of the study – the 6 minute walk test (6MWT) – did not reach statistical significance when comparing the group given AT-GAA with the ERT-naive group receiving the current standard of care, alglucosidase alfa. Results from the ERT Switch portion of the study were much more encouraging, although the overall 6MWT results still weren’t statistically significant.
When comparing forced vital capacity (FVC), between AT-GAA and the ERT-naive group, statistical significance was not seen. There was, however, statistical significance when compared with the switch group. Enough so that the overall comparison was also statistically significant.
AT-GAA is the combination of cipaglucosidase alfa (ATB200) with miglustat. Cipaglucosidase alfa is a new enzyme replacement therapy (ERT). Miglustat is a drug approved to treat Gaucher disease in the United States and Niemann-Pick disease in Europe. According to Amicus, miglustat stabilizes the effectiveness of cipaglucosidase alfa. AT-GAA has previously been granted Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) and Amicus initiated a rolling Biologics License Application in late 2020 (to read more about this, click here).
The PROPEL study was a 52-week, double-blind randomized study comparing the efficacy, safety and tolerability of AT-GAA (n = 95) with alglucosidase alfa (n = 28).
At the end of the 1-year study, overall, adults given AT-GAA walked an average of 21 meters further in the 6MWT compared to only 7 meters in adults given alglucosidase alfa. That difference is impressive but it was not considered to be statistically different because of variability. Statistical significance is more important that a comparison of means. Nevertheless, Amicus representatives have remained positive in recent statements and claim that FDA approval may still be in the near future. Investors are less optimistic. It’s important to note though, that a drug that improves on only some measures is still a potential improvement and may be a valuable treatment option.