The efficacy of cipaglucosidase alfa/miglustat co-administration on ambulatory function was measured by the 6MWT. The 6MWD, measured in meters, is the distance walked on the 6MWT. A greater distance indicated greater endurance. An increase from baseline indicated improvement.

Analysis was performed on Intent-to-treat (ITT)-observed (OBS) population. Number of participants analyzed are based on those who had 6MWD result at Week 52. In addition, 1 outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.

The efficacy of cipaglucosidase alfa/miglustat co-administration on pulmonary function was measured by sitting FVC (% predicted). FVC is a standard pulmonary function test used to quantify respiratory muscle weakness.

Analysis was performed on ITT-Last Observation Carried Forward (LOCF) population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline values and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The total score for the MMT lower extremity strength included the following 8 body parts: right/left hip flexion, right/left hip abduction, right/left knee flexion and right/left knee extension. The MMT lower extremity score ranged from 0 to 40, with lower scores indicating weaker muscle strength. An increase from baseline indicated increased muscle strength.

Analysis was performed on the ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values and 4 subjects had no post-baseline values; these subjects were not included in the analysis. In the alglucosidase alfa/placebo group, 3 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In addition, the outlier subject was not included in the analysis.

The 6MWD, measured in meters, is the distance walked on the 6MWT.

Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

Physical Function Short Form 20a (v2.0) consisted of 20 questions. The first 14 questions were each scored on a scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty; the next 6 questions were each scored on a scale from 1 to 5 as follows: 1 = cannot do; 2 = quite a lot; 3 = somewhat; 4 = very little; 5 = not at all. The total score was calculated by summing up scores (1 to 5) across all items. Total scores range from 20 to 100. A higher score represented a better outcome.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

Fatigue Short Form 8a consisted of 6 questions, each scored on a scale from 1 to 5 as follows: 1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; 5 = very much; and 2 questions, each scored on a scale from 1 to 5 as follows: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. The total score was calculated by summing up scores (1 to 5) across all items. A lower score represented lower fatigue symptoms.

Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The GSGC consisted of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers' maneuver, and arising from a chair. Results of the GSGC included the time required to complete the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair climb, and Gowers' maneuver, and 1 to 6 points for arising from a chair), and a total score. GSGC total score was the sum of the component scores from the 4 functional tests. The total score ranged from a minimum of 4 points (normal performance) to a maximum of 27 points (worst performance).

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 11 subjects had neither baseline nor post-baseline values, and 2 had no post-baseline values; these subjects were not included in the analysis. In the alglucosidase alfa/placebo group, 5 subjects had neither baseline nor post-baseline values, and 2 had no post-baseline values; these subjects were not included in the analysis. In addition, the outlier subject was not included in the analysis.

The R-PAct scale was an 18-item questionnaire to measure limitations in activities and restriction in social participation. Possible responses to questions were as follows: unable to perform, able to perform, but with difficulty, and able to perform without difficulty. The total score was calculated by summing up the observed scores across the 18 items and it ranged from 0 to 36, with higher values representing lower level of disease impact on the muscles.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 16 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In the alglucosidase alfa/placebo group, 4 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In addition, the outlier subject was not included in the analysis.

The EuroQol Visual Analogue Scale (EQ VAS) is a vertical visual analogue scale that records the respondent's own assessment of his or her overall health status at the time of completion. Scores range from 0 (the worst health you can imagine) to 100 (the best health you can imagine). Higher EQ VAS scores represent an improved sense of overall health while lower scores represent a worsening of overall health.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In the alglucosidase alfa/placebo group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In addition, the outlier subject was not included in the analysis.

SVC is a standard pulmonary function test used to quantify respiratory muscle weakness.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 2 subjects had no post-baseline values and were not included in the analysis. In the alglucosidase alfa/placebo group, 1 subject had no baseline value, 1 subject had no post-baseline values, and they were not included in the analysis. In addition, the outlier subject was not included in the analysis.

The percent predicted values of MIP were calculated as: % predicted = (actual result / predicted result)* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The percent predicted values of MEP were calculated as: % predicted = (actual result / predicted result)

* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The percent predicted values of SNIP were calculated as: % predicted = (actual result / predicted result) * 100, where the predicted results were obtained using the reference equations from Evans and Whitelaw (2009).

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The % predicted 6MWD = (actual 6MWD / predicted 6MWD) * 100. The predicted values were calculated using Enright And Sherrill 1998 Reference Equations.

Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

QMT was measured using the hand-held dynamometer. Larger values (in kg) indicated greater muscle strength.

Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the QMT parameters displayed are based upon the number of participants who had both baseline and post-baseline values for each respective QMT parameter. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.

Each manual muscle test was evaluated on a scoring scale from 0 to 5, as follows: 0 = no muscle movement; 1 = visible muscle movement, but no movement at the joint; 2 = movement at the joint, but not against gravity; 3 = movement against gravity, but not against added resistance; 4 = movement against resistance, but less than normal; 5 = normal strength. Upper extremity score was the sum of scores for right/left shoulder abduction, right/left shoulder adduction, right/left elbow extension, and right/left elbow flexion, with the total score ranging from 0 to 40.

Proximal muscle group score, the sum of scores for right/left hip flexion, right/left hip abduction, right/left shoulder abduction, and right/left shoulder adduction, with the total score ranging from 0 to 40. MMT total score was the sum of the lower and upper extremity scores and ranged from 0 to 80. Lower scores indicated lower overall muscle strength. An increase from baseline indicated improvement in muscle strength.

Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the MMT parameters displayed are based upon the number of participants who had both baseline and post-baseline values for each respective MMT parameter. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.

Maximum VC is the greater of the two VC values (FVC or SVC).

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

The Upper Extremities Short Form 7a consisted of 7 items each scored on a decreasing scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty.

Dyspnea Severity Short Form 10a consisted of 10 items each scored on a scale from 0 to 3 as follows: 0

= no shortness of breath; 1 = mildly short of breath; 2 = moderately short of breath; 3 = severely short of breath.

A total score was generated for each instrument by adding up each item. Total scores for upper extremities range from 7 to 35. Total scores for dyspnea range from 0 to 30. A higher score for upper extremities represented improvement in symptoms. A lower score for dyspnea severity represented improvement in symptoms.

Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the PROMIS total scores displayed are based upon the number of participants who had both baseline and post-baseline values for each respective PROMIS total score (PROMIS-Dyspnea and Upper Extremities Total Scores). In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.

Motor function test assessed the time to complete individual GSGC component tests (10-meter walk, 4- stair climb, Gowers' maneuver, and arise from a chair) and the TUG test. The TUG test assessed the time a subject needed to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down.

Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the GSGC components and the TUG test displayed are based upon the number of participants who had both baseline and post-baseline values for each respective GSGC component and the TUG test. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.

Physician's Global Impression of Change is based on a single item that is scored on a 7-point rating scale ranging from 1 "very much worse" to 7 "very much improved".

A tertiary response variable (improving, declining, stable) was defined as follows: "Improving", which consisted of improved, moderately improved, and very much improved; "Declining", which consisted of worse, moderately worse, and very much worse; and "Stable", which equaled to no change.

Analysis was performed on ITT-OBS population. Number of participants analyzed are based on those who had PGIC data at Week 52. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.

The SGIC is designed to record the participants' impression of their functional status since starting study drug using a 7-point scale ranging from 1 "very much worse" to 7 "very much improved".

A tertiary response variable (improving, declining, stable) was defined as follows: "Improving", which consisted of improved, moderately improved, and very much improved; "Declining", which consisted of worse, moderately worse, and very much worse; and "Stable", which equaled to no change.

Analysis was performed on ITT-OBS population. Number of participants analyzed are based on those who had SGIC data at Week 52. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.

A composite subject-level response of the 2 relevant clinical outcomes, 6MWD and FVC (% predicted), was assessed. Prespecified thresholds were used for assessment of improvement consistent with published minimal clinically important difference values for comparable instruments in similar disease.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject who had no post-baseline FVC value was counted as not improved and included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

Treatment-emergent ADAs were defined as participants who had seroconverted or boosted their preexisting ADA during the study period.

Analysis was performed on safety population which included subjects who had received at least 1 dose of study drug. Number analyzed equals participants evaluable at specified treatment.

Levels of urinary Hex4, a biomarker of disease substrate, were measured. The assay specifically targets Hex4, the glucose tetrasaccharide (Glc4), which is a biomarker of glycogen storage.

Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

Change from baseline to Week 52 in serum CK level. CK levels were measured as part of the serum chemistry panel.

Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed equals participants evaluable at specified time points.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed equals participants evaluable at specified timepoints.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed equals participants evaluable at specified timepoints.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed equals participants evaluable at specified timepoints.

A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total human acid α-glucosidase (GAA) protein signature peptide T09 and plasma miglustat determinations.

A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total GAA protein signature peptide T09 and plasma miglustat determinations.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed based upon number of subjects with evaluable data for population PK analysis at specified timepoints.

On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.

Number analyzed based upon number of subjects with evaluable data for population PK analysis at specified timepoints.