Biology:Vestronidase alfa
| Clinical data | |
|---|---|
| Trade names | Mepsevii |
| Other names | Vestronidase alfa-vjbk |
| AHFS/Drugs.com | Monograph |
| License data | |
| Routes of administration | Injection |
| ATC code | |
| Legal status | |
| Legal status |
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| 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]
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]
References
- ↑ "Vestronidase Alfa: A Review in Mucopolysaccharidosis VII". BioDrugs 33 (2): 233–240. April 2019. doi:10.1007/s40259-019-00344-7. PMID 30848434.
- ↑ Jump up to: 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 "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.
This article incorporates text from this source, which is in the public domain.
- ↑ Jump up to: 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 "Drug Trial Snapshot: Mepsevii". 4 December 2017. https://www.fda.gov/drugs/drug-trial-snapshot-mepsevii. This article incorporates text from this source, which is in the public domain.
- ↑ Jump up to: 4.0 4.1 4.2 "Mepsevii EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/mepsevii. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ (PDF) New Drug Therapy Approvals 2017 (Report). January 2018. https://www.fda.gov/media/110526/download. Retrieved 16 September 2020.
- ↑ "Mepsevii- vestronidase alfa injection". 19 November 2017. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=925d4e21-fd98-474d-a34d-a0b3558ed750.
External links
- "Vestronidase alfa". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/Vestronidase%20alfa.
- Clinical trial number NCT02230566 for "A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)" at ClinicalTrials.gov
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