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Label indication MEPSEVII is indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome). Limitations of Use The effect of MEPSEVII on the central nervous system manifestations of MPS VII has not been determined. FDA label
Also known as recombinant human beta-glucoronidase, rhGUS, Mepsevii ™, vestronidase alfa, vestronidase alfa-vjbk, recombinant human beta-glucuronidase, rh-β-glucuronidase
UX003 · 4 trials · 6 indications
An adverse event (AE) is defined as any untoward medical occurrence, whether or not considered drug related. A serious AE is an AE that at any dose, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; or is an important medical event. AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death). TEAEs were defined as reported AEs with onset during the treatment.
Baseline was defined as the average of all assessments prior to or on the date of cross-over to active treatment with UX003. (This provides the valid assessment, as placebo effect was subtracted from the treatment effect estimate providing a more conservative assessment of the true treatment effect.) Percent change from baseline in uGAG DS was analyzed by generalized estimating equation (GEE) modeling based on observed data. The GEE model included included baseline value, and the UX003 treatment week as a categorical variable. The covariance structure within subjects was assumed to be exchangeable. In the United States (US), this was considered a secondary outcome measure. Per guidance from the Food and Drug Administration (FDA), no primary efficacy variable was declared in the US. Efficacy was to be based on the totality of the clinical data on a per participant basis.
Liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate (LS-MS/MS-DS) method. For the participant previously treated with UX003 under an eIND, percent change from initial baseline was used.
Adverse event (AE): any untoward medical occurrence in a participant, whether or not considered drug related. Serious AE (SAE): an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Other important medical events may also, in the opinion of the Investigator, be considered SAEs. An AE was considered a TEAE if it occurred on or after the first dose, and was not present prior to the first dose, or it was present at the first dose but increased in severity during the study. Events recorded as either possibly, probably, or definitely related to treatment were categorized as related. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.03.
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate.
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-chondroitin sulfate.
Participants with a ≥ 50% decrease in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate or chondroitin sulfate.
Adverse Event (AE): any untoward medical occurrence in a subject, whether or not considered drug related. SAE: an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Other important medical events may also, in the opinion of the Investigator, be considered SAEs. An AE was considered a TEAE if it occurred on or after the first dose, and was not present prior to the first dose, or it was present at the first dose but increased in severity during the study. Events recorded as either possibly, probably, or definitely related to treatment were categorized as related. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.03.
| Arm | Type | Description |
|---|---|---|
| UX003 | EXPERIMENTAL | 4 mg/kg UX003 every other week (QOW) |
| Group A: 4 mg/kg UX003 | EXPERIMENTAL | 4 mg/kg UX003 QOW through Week 46 |
| Group B: 8 Weeks Placebo then 4 mg/kg UX003 | EXPERIMENTAL | Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46 |
| Group C: 16 Weeks Placebo then 4 mg/kg UX003 | EXPERIMENTAL | Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46 |
| Group D: 24 Weeks Placebo then 4 mg/kg UX003 | EXPERIMENTAL | Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46 |
| Name | Type | Description |
|---|---|---|
| UX003 | DRUG | solution for intravenous (IV) infusion |
| Placebo | OTHER | Placebo consisting of the UX003 formulation buffer (without rhGUS) |
Inclusion Criteria: * Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing. * Willing and able to provide written, signed informed consent or, in the case of subjects under the age of 18 (or 16 years, depending on the region), provide written a...
UX003 is an investigational enzyme replacement therapy being developed for mucopolysaccharidosis type 7 (MPS 7), also known as Sly syndrome. It is designed to address the underlying enzyme deficiency in this rare lysosomal storage disorder. The drug is not yet approved and remains in clinical development.
UX003 is a recombinant form of the enzyme beta-glucuronidase. MPS 7 is caused by deficient beta-glucuronidase activity, which leads to accumulation of glycosaminoglycans in tissues. By supplying a functional version of this enzyme, UX003 aims to restore its activity and help break down these accumulated substances.
UX003 is being developed by Ultragenyx Pharmaceutical Inc., a biopharmaceutical company focused on rare and ultra-rare diseases. Ultragenyx trades on the Nasdaq under the ticker symbol RARE.
UX003 has been studied in Phase 3 clinical trials for MPS 7. The Phase 3 program has been completed, and the drug remains investigational. It has not been approved by the FDA for any indication.
UX003 has been evaluated in completed clinical trials including NCT02432144 (Phase 3), NCT02230566 (Phase 3), NCT02418455 (Phase 2), and NCT01856218 (Phase 1/2). These studies enrolled patients with MPS 7 across multiple countries and assessed the safety and efficacy of enzyme replacement therapy.