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Vestronidase alfa

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Vestronidase alfa, sold under brand name Mepsevii, is a medication for the treatment of Sly syndrome.[3] 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.[4][5] MPS VII is an extremely rare, progressive condition that affects most tissues and organs.[4]

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The most common side effects after treatment with vestronidase alfa include infusion site reactions, diarrhea, rash (urticaria) and anaphylaxis (sudden, severe allergic reaction).[4][1]

The US. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[6] It was approved for use in the European Union in August 2018.[1]

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Medical uses

Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome).[1][7]

History

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

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.[5]

The benefit and side effects of vestronidase alfa were based primarily on one trial.[5] Participants were randomly assigned to four groups.[5] Three groups of participants received placebo treatment before starting vestronidase alfa treatment and one group received vestronidase alfa only.[5] vestronidase alfa or placebo were given once every two weeks as intravenous (IV) infusions.[5] Neither participants nor healthcare providers knew which treatment was given until after the trial was completed.[5]

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.[5] The 6MWT measured the distance a patient could walk on a flat surface in 6 minutes.[5] An additional follow-up using 6MWT was done for up to 120 weeks.[5]

The application for vestronidase alfa was granted fast track designation, orphan drug designation, and a rare pediatric disease priority review voucher.[4] This was the twelfth rare pediatric disease priority review voucher issued.[4]

The US Food and Drug Administration (FDA) granted approval of Mepsevii to Ultragenyx Pharmaceutical, Inc,[4] and required the manufacturer to conduct a post-marketing study to evaluate the long-term safety of the product.[4]

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References

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