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
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C3308H4996N874O940S16
Molar mass 72562.49 g·mol−1

Vestronidase alfa, sold under brand name Mepsevii, is a medication for the treatment of Sly syndrome. [4] 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. [5] [6] MPS VII is an extremely rare, progressive condition that affects most tissues and organs. [5]

Contents

The most common side effects after treatment with vestronidase alfa include infusion site reactions, diarrhea, rash (urticaria) and anaphylaxis (sudden, severe allergic reaction). [5] [2]

The US. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [7] It was approved for use in the European Union in August 2018. [2]

Medical uses

Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome). [2] [8]

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. [5] Participants received treatment with vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 164 weeks. [5] Efficacy was primarily assessed via the six-minute walk test in ten participants who could perform the test. [5] After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters. [5] Additional follow-up for up to 120 weeks suggested continued improvement in three participants and stabilization in the others. [5] Two participants in the vestronidase alfa development program experienced marked improvement in pulmonary function. [5] Overall, the results observed would not have been anticipated in the absence of treatment. [5] The effect of vestronidase alfa on the central nervous system manifestations of MPS VII has not been determined. [5]

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. [6]

The benefit and side effects of vestronidase alfa were based primarily on one trial. [6] Participants were randomly assigned to four groups. [6] Three groups of participants received placebo treatment before starting vestronidase alfa treatment and one group received vestronidase alfa only. [6] vestronidase alfa or placebo were given once every two weeks as intravenous (IV) infusions. [6] Neither participants nor healthcare providers knew which treatment was given until after the trial was completed. [6]

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. [6] The 6MWT measured the distance a patient could walk on a flat surface in 6 minutes. [6] An additional follow-up using 6MWT was done for up to 120 weeks. [6]

The application for vestronidase alfa was granted fast track designation, orphan drug designation, and a rare pediatric disease priority review voucher. [5] This was the twelfth rare pediatric disease priority review voucher issued. [5]

The US Food and Drug Administration (FDA) granted approval of Mepsevii to Ultragenyx Pharmaceutical, Inc, [5] and required the manufacturer to conduct a post-marketing study to evaluate the long-term safety of the product. [5]

Related Research Articles

<span class="mw-page-title-main">Sly syndrome</span> 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.

<span class="mw-page-title-main">Mucopolysaccharidosis</span> 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.

<span class="mw-page-title-main">Glycogen storage disease type II</span> Medical condition

Glycogen storage disease type II(GSD-II), also called Pompe disease, and formerly known as GSD-IIa or Limb–girdle muscular dystrophy2V, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme (GAA). The inability to breakdown glycogen within the lysosomes of cells leads to progressive muscle weakness throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and the nervous system.

Iduronidase, sold as Aldurazyme, is an enzyme with the systematic name glycosaminoglycan α-L-iduronohydrolase. It catalyses the hydrolysis of unsulfated α-L-iduronosidic linkages in dermatan sulfate.

Mepolizumab, sold under the brand name Nucala by GlaxoSmithKline, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome (HES). It recognizes and blocks interleukin-5 (IL-5), a signalling protein of the immune system.

Emil Kakkis is an American medical geneticist known for his work to develop treatments for ultra rare disorders. He is the Founder of the Everylife Foundation for Rare Disease and Founder, CEO and President of Ultragenyx Pharmaceutical Inc.

Elosulfase alfa, sold under the brand name Vimizim, is a medication used for the treatment of Morquio syndrome which is caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase. Elosulfase alfa is a synthetic version of this enzyme.

<span class="mw-page-title-main">Fostemsavir</span> Chemical compound

Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.

Evinacumab, sold under the brand name Evkeeza, is a monoclonal antibody medication for the treatment of homozygous familial hypercholesterolemia (HoFH).

Sebelipase alfa, sold under the brand name Kanuma, is a recombinant form of the enzyme lysosomal acid lipase (LAL) that is used as a medication for the treatment of lysosomal acid lipase deficiency (LAL-D). It is administered via intraveneous infusion. It was approved for medical use in the European Union and in the United States in 2015.

<span class="mw-page-title-main">Trofinetide</span> Pharmaceutical drug

Trofinetide, sold under the brand name Daybue, is a medication used for the treatment of Rett syndrome. It is taken by mouth.

Cerliponase alfa, marketed as Brineura, is an enzyme replacement treatment for Batten disease, a neurodegenerative lysosomal storage disease. Specifically, Cerliponase alfa is meant to slow loss of motor function in symptomatic children over three years old with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). The disease is also known as tripeptidyl peptidase-1 (TPP1) deficiency, a soluble lysosomal enzyme deficiency. Approved by the United States Food and Drug Administration (FDA) on 27 April 2017, this is the first treatment for a neuronal ceroid lipofuscinosis of its kind, acting to slow disease progression rather than palliatively treat symptoms by giving patients the TPP1 enzyme they are lacking.

Givosiran, sold under the brand name Givlaari, is a medication used for the treatment of adults with acute hepatic porphyria. Givosiran is a small interfering RNA (siRNA) directed towards delta-aminolevulinate synthase 1 (ALAS1), an important enzyme in the production of heme.

Velmanase alfa, sold under the brand name Lamzede, is a medication used for the treatment of alpha-mannosidosis. Velmanase alfa is a recombinant human lysosomal alpha-mannosidase.

Ropeginterferon alfa-2b, sold under the brand name Besremi, is a medication used to treat polycythemia vera. It is an interferon. It is given by injection.

Lumasiran, sold under the brand name Oxlumo, is a medication for the treatment of primary hyperoxaluria type 1 (PH1).

<span class="mw-page-title-main">Ultragenyx</span> American biopharmaceutical company

Ultragenyx Pharmaceutical Inc. is an American biopharmaceutical company involved in the research and development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

Avalglucosidase alfa, sold under the brand name Nexviazyme, is an enzyme replacement therapy medication used for the treatment of glycogen storage disease type II.

Efgartigimod alfa, sold under the brand name Vyvgart, is a medication used to treat myasthenia gravis. Efgartigimod alfa is a neonatal Fc receptor blocker and is a new class of medication. It is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood. The medication causes a reduction in overall levels of IgG, including the abnormal acetylcholine receptor (AChR) antibodies that are present in myasthenia gravis. It is also available coformulated with hyaluronidase.

Cipaglucosidase alfa, sold under the brand name Pombiliti, and used in combination with miglustat, is a medication used for the treatment of glycogen storage disease type II. Cipaglucosidase alfa is a recombinant human acid α-glucosidase enzyme replacement therapy that provides an exogenous source of acid α-glucosidase.

References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  2. 1 2 3 4 "Mepsevii EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 28 February 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ↑ "Mepsevii PI". Union Register of medicinal products. 27 August 2018. Retrieved 29 June 2024.
  4. ↑ 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.
  5. 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.svg This article incorporates text from this source, which is in the public domain .
  6. 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.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
  8. ↑ "Mepsevii- vestronidase alfa injection". DailyMed. 19 November 2017. Retrieved 5 August 2020.
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