Explore The Data

PROPEL: 52-week data

ERT-subgroup analysis: prespecified

PROPEL study design1-3

Nearly 80% of the study population was ERT-experienced

PROPEL: Study design infographic
  • Primary endpoint: Change from baseline to Week 52 in 6-minute walk distance (6MWD) for comparison of superiority3‡
  • Key secondary endpoint: Change from baseline to Week 52 in forced vital capacity (FVC)3
  • POMBILITI in combination with OPFOLDA is not approved for use in ERT-naïve patients with LOPD. The ERT-naïve patient subgroup enrolled too few patients to conclusively interpret the data1,3

Select inclusion criteria1-3

  • ≥18 years of age weighing ≥40 kg at screening
  • Confirmed diagnosis of LOPD
  • ERT-experienced adults were on either US-approved or non-US-approved alglucosidase alfa for ≥24 months
  • Sitting percent-predicted FVC of ≥30% of the predicted value for healthy adults
  • 6MWD of ≥75 meters at 2 screening tests

Key exclusion criteria1-3

  • Received previous treatment with any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days, or 5 half-lives of the therapy, before Day 1 of the study, whichever was longer
  • Received gene therapy for Pompe disease
  • Use of ventilation support for more than 6 hours per day while awake

*After database lock, 1 ERT-naïve subject was found to have intentionally underperformed at baseline. This subject was excluded from all 6MWD efficacy results; this change did not alter the statistical outcomes of the study.4

†Dosage based on patient weight.2

‡Primary endpoint for superiority was not met.3

Baseline characteristics

Nearly 80% of the study population was ERT-experienced

Minimum treatment time for inclusion was 2 years

PROPEL: Baseline characteristics of patients table
PROPEL: Baseline characteristics of patients table

*After database lock, 1 ERT-naïve subject was found to have intentionally underperformed at baseline. This subject was excluded from all 6MWD efficacy results; this change did not alter the statistical outcomes of the study.4

†Dosage based on patient weight.2

‡Primary endpoint for superiority was not met.3

POMBILITI + OPFOLDA patients walked farther1,2*

6MWD mean change from baseline (± SE)

PROPEL: Figure of 6-minute walk distance (6MWD) changes from baseline to week 52

*The primary efficacy endpoint in PROPEL, change in 6MWD at 52 weeks in the POMBILITI + OPFOLDA arm versus the comparator arm, was not met.3

†A US-approved alglucosidase alfa product was not used in this clinical trial. Conclusions cannot be drawn from this clinical trial regarding comparative effectiveness between a US-approved alglucosidase alfa product and POMBILITI in combination with OPFOLDA.1,2

‡For the ERT-experienced group, the treatment difference of the mean was estimated by nonparametric analysis of covariance that included treatment, gender, baseline 6MWD, age, weight, and height in the model. Missing data at Week 52 was imputed using last observed values.1,2

POMBILITI + OPFOLDA patients’ lung function improved1,2*

Percent predicted (PP) forced vital capacity (FVC) in patients treated with POMBILITI + OPFOLDA1,2

PROPEL: Figure of Forced Vital Capacity (FVC) results from baseline to week 52
PROPEL: Figure of Forced Vital Capacity (FVC) results from baseline to week 52

*The primary efficacy endpoint in PROPEL, change in 6MWD at 52 weeks in the POMBILITI + OPFOLDA arm versus the comparator arm, was not met.3

†For the ERT-experienced group, the treatment difference of the mean was estimated by analysis of covariance that included treatment, gender, baseline FVC, age, weight, and height in the model. Missing data at Week 52 was imputed using last observed values.1,2

POMBILITI + OPFOLDA patients had improved biomarkers1,2

POMBILITI + OPFOLDA reduced Hex4 levels in ERT-experienced patients vs the comparator at 52 weeks1

PROPEL: Figure of Hex4 changes from baseline to week 52
PROPEL: Figure of Hex4 changes from baseline to week 52

Hex4 is a metabolite of excess glycogen and is measured by Glc4 concentration.1

 

ERT, enzyme replacement therapy; Glc4, glucosidase tetrasaccharide; Hex4, hexose tetrasaccharide; SD, standard deviation.

ERT-experienced population

Additional secondary endpoint scores in patients treated with POMBILITI + OPFOLDA (LS mean treatment difference from baseline)1,2

PROPEL: Figure of additional secondary endpoint scores
PROPEL: Figure of additional secondary endpoint scores

Demonstrated safety profile in 151 patients across 3 clinical trials1,2

PROPEL: Adverse reactions table
PROPEL: Adverse reactions table

A total of 5 patients across 3 clinical trials PERMANENTLY DISCONTINUED POMBILITI + OPFOLDA due to adverse reactions (4/5 due to serious adverse reactions)1

Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in POMBILITI-treated patients1

  • In clinical trials, 41 (27%) POMBILITI-treated patients experienced hypersensitivity reactions, including 4 (3%) reporting severe hypersensitivity reactions and 4 (3%) additional patients who experienced anaphylaxis1*
  • Infusion-associated reactions were reported in 48 (32%) patients treated with POMBILITI + OPFOLDA across 3 clinical trials1
  • There was no identified clinically significant effect of antidrug antibodies (ADAs) on POMBILITI + OPFOLDA PK or PD over the treatment duration of 52 weeks in PROPEL. Due to the small number of patients with negative ADA, the effect of ADA on the effectiveness of POMBILITI + OPFOLDA is unknown1

*Fulfilling at least one of the Sampson criteria.1

Open-label extension (OLE): 104-week data

ERT-subgroup analysis: prespecified from PROPEL

OLE study design

PROPEL Open-Label Extension (OLE): Interim analysis evaluating the long-term efficacy and safety of POMBILITI + OPFOLDA for an additional 52 weeks5

  • After 52 weeks in the PROPEL study, 91 ERT-experienced patients and 28 ERT-naïve patients continued or crossed over to POMBILITI + OPFOLDA*†
  • Patients in the OLE study received POMBILITI + OPFOLDA every 2 weeks, beginning 2 weeks after the last dose of the ERT that they received in the PROPEL study
  • Baseline characteristics in PROPEL were representative of the LOPD population and generally similar between
    treatment groups
OLE: Study design infographic
OLE: Study design infographic

Select Endpoints5

  • Motor function: 6MWD (% predicted)
  • Respiratory function: FVC (sitting, % predicted)
  • Biomarkers: Hex4 (mmol/mol) and CK (U/L)

* POMBILITI in combination with OPFOLDA is not approved for use in ERT-naïve patients with LOPD. The ERT-naïve patient subgroup in PROPEL enrolled too few patients to conclusively interpret the data.1,3

† ERT‑experienced patients are defined as those treated with ERT for at least 2 years prior to their participation in the PROPEL study.3

‡ Dosage based on patient weight.1,2

§ A US-approved alglucosidase alfa product was not used in this clinical trial. Conclusions cannot be drawn from this clinical trial regarding comparative effectiveness between a US-approved alglucosidase alfa product and POMBILITI in combination with OPFOLDA.1,2

‖ Includes 1 patient who enrolled but was never dosed.5

11 patients discontinued due to withdrawn consent, adverse events, investigator decision, or because they were lost to follow-up.5

Important study limitations5

  • The OLE was unblinded and had no control group
  • This study includes data that are not in the FDA-approved Prescribing Informations for POMBILITI + OPFOLDA
  • Data were analyzed descriptively, with no statistical comparisons. Therefore, no conclusions regarding treatment differences should be made as results could represent chance findings
  • LOPD is a rare disease, so the sample size was relatively small
  • Given the heterogeneous nature of LOPD, spanning a wide spectrum of manifestations, disease severity, rates of progression, and responses to treatment, tailoring the individualized treatment approaches to optimize patient outcomes will become more critical
  • Creatine kinase (CK) is a nonspecific biomarker of muscle damage. The clinical relevancy of CK has not been established in LOPD6

6-Minute Walk Distance (6MWD)

Mean (± SE) change from PROPEL baseline in PP 6MWD in ERT-experienced adults with LOPD5

OLE: Figure of 6MWD results from PROPEL baseline to week 104 in the OLE

*The primary efficacy endpoint in PROPEL, change in 6MWD at 52 weeks in the POMBILITI + OPFOLDA arm versus the comparator arm, was not met.

OLE: Table of 6MWD change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)
OLE: Table of 6MWD change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)

Forced vital capacity (FVC)

Percent predicted (PP) FVC results over 104 weeks5

OLE: Figure of FVC results from PROPEL baseline to week 104 in the OLE
OLE: Figure of FVC results from PROPEL baseline to week 104 in the OLE
OLE: Table of FVC change from baseline to week 52 (PROPEL) and week 52 to 104 (OLE)
OLE: Table of FVC change from baseline to week 52 (PROPEL) and week 52 to 104 (OLE)

Biomarker: Hex4 levels

Hex4 is a metabolite of excess glycogen and is measured by Glc4 concentration. Elevated Hex4 levels may be indicative of Pompe disease1

OLE: Figure of Hex4 results from PROPEL baseline to week 104 in the OL
OLE: Figure of Hex4 results from PROPEL baseline to week 104 in the OL
OLE: Table of Hex4 change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)
OLE: Table of Hex4 change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)

Biomarker: serum creatine kinase (CK) levels

CK is a biomarker for muscle damage6*

OLE: Figure of serum CK results from PROPEL baseline to week 104 in the OLE

*The clinical relevancy of changes in CK levels has not been established in LOPD.

OLE: Table of serum CK change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)
OLE: Table of serum CK change from baseline to week 52 (PROPEL) and week 52 to week 104 (OLE)
OLE Data: Lower Extremity, Physical Function, and Fatigue Secondary Endpoints
OLE Data: Lower Extremity, Physical Function, and Fatigue Secondary Endpoints

Safety profile: no new safety signals were identified during the OLE3

  • Most TEAEs were mild to moderate in severity
  • The most common TEAEs were headache, diarrhea, pyrexia, fatigue, and nausea
  • Five patients withdrew from the study due to TEAEs experienced during the OLE
OLE: Adverse reactions table
OLE: Adverse reactions table

*Includes data from patients treated with POMBILITI + OPFOLDA in PROPEL who may or may not have continued POMBILITI + OPFOLDA in the OLE, including data from both PROPEL and the OLE.4

†Includes data from the OLE only.5

POMBILITI + OPFOLDA. Working together.

REQUEST A REP

START A PATIENT

Sign up for emails

Sign up to receive updates about LOPD and POMBILITI + OPFOLDA

6MWD, 6-minute walk distance; Alg, alglucosidase alfa; CI, confidence interval; Cipa, cipaglucosidase alfa; CK, creatine kinase; ERT, enzyme replacement therapy; FVC, forced vital capacity; Glc4, glucosidase tetrasaccharide; GSGC, Gait, Stairs, Gowers’ maneuver, Chair; Hex4, hexose tetrasaccharide; IARs, infusion-associated reactions; IU, international units; IV, intravenous; LOPD, late-onset Pompe disease; LS, least squares; MEP, maximal expiratory pressure; Mig, miglustat; MIP, maximal inspiratory pressure; MMT, manual muscle test; OLE, open-label extension; PD, pharmacodynamics; PK, pharmacokinetics; PP, percent predicted; PROMIS, Patient-Reported Outcomes Measurement Information System; SD, standard deviation; SNIP, sniff nasal inspiratory pressure; TEAEs, treatment-emergent adverse events.