New Medicines

Glycogen storage disease type II (Pompe disease) - first-line with miglustat


New molecular entity
Amicus Therapeutics
Amicus Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
May 22Amicus announces FDA has extended review period by 90 das for its biologics license application. The revised PUFDA date for cipaglucosidase alfa is 29 August 2022 and a later date of 29 October 2022 is anticipated for the enzyme stabiliser miglustat (although the company expected the FDA to approve the applications together)[14].
Dec 21Amicus announces that the EMA has validated the MAA for AT-GAA. Validation of the application confirms the submission is accepted, and the EMA’s centralized procedure with Committee for Medicinal Products for Human Use (CHMP)’s assessment begins [13]
Sep 21US FDA accept Biologics License Application submission with a Prescription Drug User Fee Act action date of July 29, 2022, for the BLA.[11]
Jun 21EAMS scientific opinion issued to Amicus Therapeutics UK Limited for cipaglucosidase alfa with miglustat in the treatment of adult patients with late-onset Pompe disease previously treated with alglucosidase alfa [9].
May 21Amicus announces completion of successful Type B BLA meeting with the FDA [10]
Feb 21Although AT-GAA failed to meet its primary endpoint of six-minute walk test in PIII study, Amicus are still planning for filings based on data showing that AT-GAA has a statistical advantage over Sanofi´s Lumizyme [8].
Dec 20Initiation of rolling BLA submission. Amicus submitted the non-clinical component of the cipaglucosidase alfa BLA and will submit the chemistry, manufacturing and controls (CMC) component, and the final clinical module in the first half of 2021 [10]
May 20Top line data from the pivotal study (NCT03729362) is expected in the first half of 2021, and Amicus have agreed a rolling BLA submission with the FDA timetabled to start H2 2020 and complete H1 2021. EU MAA will be submitted in 2021 [7].
Feb 19Granted breakthrough therapy designation (BTD) in the US for late onset Pompe disease [3]
Sep 18the proposed PIII pivotal study has also been discussed with the FDA. The company also discussed prospects for Accelerated Approval: the current data package was not considered sufficient by the FDA to support this, however the company intends to continue discussions as further data become available [4].
Jun 18Amicus announces that it has received advice from the EMA on a pathway to regulatory approval in the EU, including design of the pivotal PIII study. The EMA considers the efficacy data currently available promising but inadequate for conditional approval: Amicus intends to continue dialogue with the EMA on conditional approval based on forthcoming data from the current PI/II study programme [4].


Enzyme replacement therapy. Highly targeted rhGAA (ATB200) is co-administered with a chaperone (AT2221, miglustat).
The overall prevalence has been estimated at 1 in 40,000, with 1 in 138,000 for the infantile form and 1 in 57,000 for the adult form [1].
Glycogen storage disease type II (Pompe disease) - first-line with miglustat

Further information


Trial or other data

Nov 21PIII PROPEL RCT (n=125) found cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6min walk distance in overall population at week 52 (change from baseline: 20.8 vs. 7.2m, respectively) [12].
Feb 21PIII PROPEL study did not achieve primary endpoint. At week 52, subjects who received AT-GAA could walk 21 meters further than at baseline, compared to a 7 meter improvement in the Lumizyme group (this difference was not statistically significant). However, lung function decline was 1% with AT-GAA vs. 4% in the Lumizyme cohort (p=0.023). Differences were more pronounced in patients who had previously received enzyme replacement therapy [8].
Oct 19the open-label extension study (NCT04138277) will examine safety and efficacy up to four years from baseline, with final outcome data expected Dec 2023 [6].
Dec 18PIII PROPEL study initiated (NCT03729362) to compare ATB200 + miglustat with alglucosidase alfa plus placebo and the first patient dosed. In the double-blind trial (estimated n=100), patients will be randomised to ATB200 plus miglustat or alglucosidase plus placebo for 12 months with the option to continue in an open label extension study; primary outcome is the six-minute walk test, and estimated primary completion date December 2020 [5].
Jan 16International, multi-centre, PII study of 32 Pompe disease patients that are currently receiving enzyme-replacement therapy (ERT) starts (NCT02675465). The purpose of this study is to find out if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease. Patients will be recruited from the US, Germany, Netherlands and UK. Collection of primary outcome data due to complete Sep 19 [2].

Evidence based evaluations