Vestronidase alfa

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Vestronidase alfa
Clinical data
Trade names Mepsevii
Other namesVestronidase alfa-vjbk
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Injection
ATC code
Legal status
Legal status
  • US: ℞-only
  • EU:Rx-only
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
UNII
KEGG
Chemical and physical data
Formula C3308H4996N874O940S16
Molar mass 72562.49 g·mol−1

Vestronidase alfa, sold under brand name Mepsevii, is a drug for the treatment of Sly syndrome. [1] It is a recombinant form of the human enzyme beta-glucuronidase. It was approved in the United States in November 2017, to treat children and adults with an inherited metabolic condition called mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome. [2] [3] MPS VII is an extremely rare, progressive condition that affects most tissues and organs. [2]

Contents

The most common side effects after treatment with vestronidase alfa include infusion site reactions, diarrhea, rash (urticaria) and anaphylaxis (sudden, severe allergic reaction). [2] [4]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [5] It was approved for use in the European Union in August 2018. [4]

Medical uses

Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome). [4] [6]

History

The safety and efficacy of vestronidase alfa were established in a clinical trial and expanded access protocols enrolling a total of 23 participants ranging from five months to 25 years of age. [2] Participants received treatment with vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 164 weeks. [2] Efficacy was primarily assessed via the six-minute walk test in ten participants who could perform the test. [2] After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters. [2] Additional follow-up for up to 120 weeks suggested continued improvement in three participants and stabilization in the others. [2] Two participants in the vestronidase alfa development program experienced marked improvement in pulmonary function. [2] Overall, the results observed would not have been anticipated in the absence of treatment. [2] The effect of vestronidase alfa on the central nervous system manifestations of MPS VII has not been determined. [2]

The FDA approved vestronidase alfa-vjbk based primarily on evidence from one clinical trial (NCT02230566) of 12 participants with mucopolysaccharidosis VII. The trial was conducted at four sites in the United States. [3]

The benefit and side effects of vestronidase alfa were based primarily on one trial. [3] Participants were randomly assigned to four groups. [3] Three groups of participants received placebo treatment before starting vestronidase alfa treatment and one group received vestronidase alfa only. [3] vestronidase alfa or placebo were given once every two weeks as intravenous (IV) infusions. [3] Neither participants nor healthcare providers knew which treatment was given until after the trial was competed. [3]

The benefit of 24 weeks of vestronidase alfa treatment was primarily evaluated by the 6-minute walking test (6MWT) and compared to placebo treatment in ten participants who could perform the test. [3] The 6MWT measured the distance a patient could walk on a flat surface in 6 minutes. [3] An additional follow-up using 6MWT was done for up to 120 weeks. [3]

The application for vestronidase alfa was granted fast track designation, orphan drug designation, and a rare pediatric disease priority review voucher. [2] This was the twelfth rare pediatric disease priority review voucher issued. [2]

The U.S. Food and Drug Administration (FDA) granted approval of Mepsevii to Ultragenyx Pharmaceutical, Inc, [2] and required the manufacturer to conduct a post-marketing study to evaluate the long-term safety of the product. [2]

Related Research Articles

Sly syndrome Medical condition

Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules called glycosaminoglycans. The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely.

Mucopolysaccharidosis Medical condition

Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cells that help build bone, cartilage, tendons, corneas, skin and connective tissue. GAGs are also found in the fluids that lubricate joints.

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References

  1. ↑ McCafferty EH, Scott LJ (April 2019). "Vestronidase Alfa: A Review in Mucopolysaccharidosis VII". BioDrugs. 33 (2): 233–240. doi:10.1007/s40259-019-00344-7. PMC   6469592 . PMID   30848434.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "FDA approves treatment for rare genetic enzyme disorder" (Press release). U.S. Food and Drug Administration (FDA). 15 November 2017. Archived from the original on 10 December 2019. Retrieved 9 December 2019.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  3. 1 2 3 4 5 6 7 8 9 10 "Drug Trial Snapshot: Mepsevii". U.S. Food and Drug Administration (FDA). 4 December 2017. Archived from the original on 10 December 2019. Retrieved 9 December 2019.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  4. 1 2 3 "Mepsevii EPAR". European Medicines Agency (EMA). Retrieved 28 February 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ↑ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
  6. ↑ "Mepsevii- vestronidase alfa injection". DailyMed. 19 November 2017. Retrieved 5 August 2020.
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