MEPSEVII® (vestronidase alfa-vjbk) demonstrated improvement or stabilization across multiple measures1

Mobility

Patients treated with MEPSEVII had improved or stabilized mobility1

6-minute walk test (6MWT)2

  • A measure for assessing the compounded impact of multisystem clinical manifestations on the performance of activities of daily living

Observed individual improvement in 6MWT in 3 of the 10 patients who could perform the test1

Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) with MPS VII were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT).1,2

Study 202 ‑ Extension trial (additional 144 weeks after week 48): Patients who were enrolled in the 48-week study were eligible to roll over to an open-label extension study in which patients received additional doses of MEPSEVII 4 mg/kg intravenously every other week for up to 144 weeks.1

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate
  • This resulted in a heterogeneous group
  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

Observed stabilization in 6MWT1

A solid line indicates the unassisted assessments, and a dotted line indicates the assisted assessments.

Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) with MPS VII were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT).1,2

Study 202 ‑ Extension trial (additional 144 weeks after week 48): Patients who were enrolled in the 48-week study were eligible to roll over to an open-label extension study in which patients received additional doses of MEPSEVII 4 mg/kg intravenously every other week for up to 144 weeks.1

3 of 7 patients used a walking device1

  • Patient 10 did not use an assistive device at baseline but started using an assistive device postbaseline from treatment week 8
  • Patients 6 and 9 consistently used an assistive device

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate
  • This resulted in a heterogeneous group
  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

Mean difference in 6MWT between MEPSEVII and placebo treatmenta,b

Number and treatment assignment of patients included in analysis: 5 placebo period; 8 MEPSEVII period.

aANCOVA analysis of change from baseline in least squares (LS) mean between placebo and MEPSEVII for different periods, after adjusting for study cohort, age, and baseline 6MWT distance. Patients who used walking devices were imputed as zeros in the analysis.

bNumber and treatment assignment of patients included in the analysis was based upon a randomized-start trial design and patient ability to complete testing. Due to no placebo period for the 3 patients who received 48 weeks of MEPSEVII in the first cohort of the randomized-start design, more data were available for analyses during the treatment period (n=8) than during the placebo period (n=5). 

Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis VII (MPS VII).1,2

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate
  • This resulted in a highly heterogeneous group
  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

6-minute walk test (6MWT)2

  • A measure for assessing the compounded impact of multisystem clinical manifestations on the performance of activities of daily living

Observed individual improvement in 6MWT in 3 of the 10 patients who could perform the test1


Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) with MPS VII were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT). 1,2

Study 202 ‑ Extension trial (additional 144 weeks after week 48): Patients who were enrolled in the 48-week study were eligible to roll over to an open-label extension study in which patients received additional doses of MEPSEVII 4 mg/kg intravenously every other week for up to 144 weeks.1

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate

  • This resulted in a heterogeneous group

  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level
    of cognition

Observed stabilization in 6MWT1

A solid line indicates the unassisted assessments, and a dotted line indicates the assisted assessments.

Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) with MPS VII were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT).1,2

Study 202 ‑ Extension trial (additional 144 weeks after week 48): Patients who were enrolled in the 48-week study were eligible to roll over to an open-label extension study in which patients received additional doses of MEPSEVII 4 mg/kg intravenously every other week for up to 144 weeks.1

3 of 7 patients used a walking device1

  • Patient 10 did not use an assistive device at baseline but started using an assistive device postbaseline from treatment week 8

  • Patients 6 and 9 consistently used an assistive device

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate

  • This resulted in a heterogeneous group

  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

Mean difference in 6MWT between MEPSEVII and placebo treatmenta,b

Number and treatment assignment of patients included in analysis: 5 placebo period; 8 MEPSEVII period.

aANCOVA analysis of change from baseline in least squares (LS) mean between placebo and MEPSEVII for different periods, after adjusting for study cohort, age, and baseline 6MWT distance. Patients who used walking devices were imputed as zeros in the analysis.

bNumber and treatment assignment of patients included in the analysis was based upon a randomized-start trial design and patient ability to complete testing. Due to no placebo period for the 3 patients who received 48 weeks of MEPSEVII in the first cohort of the randomized-start design, more data were available for analyses during the treatment period (n=8) than during the placebo period (n=5). 

Study 301 ‑ Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) were assessed to evaluate the efficacy and safety of recombinant human β-glucuronidase (rhGUS) enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis VII (MPS VII).1,2

Small heterogeneous patient group1

  • The extremely small population of patients with MPS VII globally necessitated the enrollment of all patients able to participate
  • This resulted in a highly heterogeneous group
  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

Respiratory

MEPSEVII demonstrated improvement in pulmonary function after 120 weeks of treatment1

Improvement in pulmonary function from baseline

21% improvement in FVC (% predicted) in 1 patient1

Study 201 - Ex-US investigation (120 weeks): A single-arm, open-label, dose-exploration study outside the United States included 3 patients with MPS VII aged 5 to 25 years. FVC = forced vital capacity.

Mobility in this patient also improved1

  • 105-meter improvement in the 6MWT in the same patient

Small heterogeneous patient group1

  • Due to the extremely small population of patients with MPS VII, the patient group was heterogeneous
  • Clinical end points in some patients were not assessable due to the extent of disease, age, or level of cognition

Organ function

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Organ function

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Study 301 - Randomized Start trial (Baseline to 48 weeks): The efficacy study was a randomized-start, phase 3 clinical study in which 12 patients (4 males, 8 females) aged 8 to 25 years (median age: 14 years) were assessed to evaluate the efficacy and safety of recombinant human ß-glucuronidase (rhGUS) enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis VII (MPS VII).1,2

Study 203 - Open-label, single arm (48 weeks): An open-label, uncontrolled single arm study in which 8 patients below 5 years of age received MEPSEVII at 4 mg/kg every 2 weeks for 48 weeks with an optional 240 weeks of additional dose continuation period.1

Study 201 - Ex-US investigation (120 weeks): A single-arm, open-label, dose-exploration study outside the United States included 3 patients with MPS VII aged 5 to 25 years.1

Small heterogeneous patient group1

  • Due to the extremely small population of patients with MPS VII, the patient group was heterogeneous

INDICATION
MEPSEVII is a recombinant human lysosomal beta glucuronidase 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.

BOXED WARNING AND ADDITIONAL IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS

  • Anaphylaxis has occurred with MEPSEVII administration, as early as the first dose, therefore appropriate medical support should be readily available when MEPSEVII is administered.
  • Closely observe patients during and for 60 minutes after MEPSEVII infusion.
  • Immediately discontinue the MEPSEVII infusion if the patient experiences anaphylaxis.
  • Anaphylaxis to MEPSEVII was reported in 2 of 20 patients in the clinical program. The two patients with anaphylaxis to MEPSEVII during the clinical trials had one occurrence each and tolerated subsequent infusions of MEPSEVII, without recurrence.
  • Consider the risks and benefits of re-administering MEPSEVII following anaphylaxis
  • Manifestations included respiratory distress, cyanosis, decreased oxygen saturation, and hypotension.
  • Prior to discharge, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur.

Adverse Reactions

  • In a clinical trial, the most common adverse reactions occurring with MEPSEVII treatment included infusion site extravasation, diarrhea, rash, anaphylaxis, infusion site swelling, peripheral swelling, and pruritus.
  • One patient experienced a febrile convulsion during MEPSEVII treatment. The patient subsequently was re-challenged without recurrence and continued on treatment.

Use in Specific Populations

  • There are no available data on MEPSEVII use in pregnant women to determine a drug-associated risk of adverse developmental outcomes.
  • There are no data on the presence of MEPSEVII in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Ultragenyx at 1-888-756-8657.
Please see full Prescribing Information, including the BOXED WARNING, for a complete discussion of the risks associated with MEPSEVII.

References: 1. MEPSEVII [package insert]. Novato, CA: Ultragenyx Pharmaceutical Inc; 2020. 2. Data on file. Clinical Study Report UX003-CL301. Ultragenyx Pharmaceutical Inc; January 9, 2017.