The company also remains on track to file a biologics license application (BLA) with the U.S. Food and Drug Administration (FDA) requesting the approval of AT-GAA to treat those with late-onset Pompe in the beginning of 2021.
AT-GAA contains a man-made, optimized form of the enzyme acid alpha-glucosidase (GAA) called cipaglucosidase alfa (ATB200) that is administered together with an oral small molecule called miglustat (AT2221) that works as a pharmacological chaperone. Together, these two molecules aim to restore function and increase the stability of GAA, which is faulty in patients with Pompe.
The safety and effectiveness of AT-GAA are currently being investigated in the Phase 3 PROPEL trial (NCT03729362) in adults with late-onset Pompe disease. During the fourth quarter of 2019, Amicus achieved and exceeded its target enrollment goal of 100 patients. The study now has 123 participants recruited from 59 clinical sites worldwide.
PROPEL is a 52-week, randomized, double-blind, Phase 3 trial designed to assess and compare the safety, tolerability and effectiveness of AT-GAA to alglucosidase alfa (marketed as Lumizyme by Sanofi Genzyme in the U.S.), an enzyme replacement therapy (ERT) that is currently considered the standard of care for patients with late-onset Pompe.
The study will assess whether AT-GAA may be superior to a combination of alglucosidase alfa with an oral placebo in patients who previously had been treated with ERT, as well as in those who had not (ERT naïve).
The trial’s main goal is to evaluate changes from baseline to the end of the 52-week treatment period in six-minute walk distance (an integrated measure of disease progression that takes into account an individual’s heart and lung fucntion). Secondary goals include changes in measures of lung and motor function and muscle strength.
The FDA previously granted the designation of breakthrough therapy to AT-GAA for the treatment of late-onset Pompe based on promising findings from a Phase 1/2 trial (NCT02675465), showing that treated patients experienced significant improvements in six-minute walk distance.
Based on the same findings, the British Medicines and Healthcare products Regulatory Agency (MHRA) has now granted the designation of Promising Innovative Medicine (PIM) to AT-GAA. By receiving this designation, a medication becomes eligible for the Early Access to Medicines Scheme (EAMS), which allows patients with serious or life-threatening disorders to have access to medicines that have the potential to address an unmet medical need.
“Regulatory agencies in the U.S. and now the U.K., have recognized the highly differentiated clinical data set and the great potential for AT-GAA to meet the currently unmet medical needs in Pompe disease through the granting of Breakthrough Therapy Designation and the Promising Innovative Medicine Designation, respectively,” John F. Crowley, chairman and CEO of Amicus, said in a press release.
“Amicus now plans to apply for and initiate a rolling submission of the AT-GAA BLA in the U.S. later this year. These designations, together with the results from the Phase 2 study and the now fully enrolled PROPEL pivotal study, support our strategy to advance AT-GAA as quickly as possible with the potential to become the new standard of care for all persons living with Pompe disease,” Crowley said.
A rolling submission will enable the company to file portions of the regulatory application to the FDA gradually as they are completed, instead of waiting for the completion of all BLA sections for the final submission.
Amicus and its key strategic partner, WuXi Biologics, also have initiated the process performance qualification (PPQ) runs that will provide the basis for the Chemistry, Manufacturing, and Control (CMC) module for the BLA submission.
The manufacturing focus on AT-GAA will support ongoing and future clinical studies. WuXi Biologics also will support Amicus with its dual sourcing strategy and manufacture at two sites, including its new facility in Ireland, which is continuing as planned.