General Information

Mepsevii (vestronidase alfa-vjbk) is a recombinant human lysosomal beta glucuronidase. MPS VII is a lysosomal storage disorder caused by deficiency of an enzyme called beta-glucuronidase, which causes an abnormal buildup of toxic materials in the body's cells. Mepsevii is an enzyme replacement therapy that works by replacing the missing enzyme.

Mepsevii is specifically indicated for pediatric and adult patients for the treatment of Mucopolysaccharidosis VII.

Mepsevii is supplied as a solution for intravenous infusion. Mepsevii should be administered under the supervision of a healthcare professional with the capability to manage anaphylaxis. Premedication is recommended 30 to 60 minutes prior to the start of the infusion. The recommended dosage of Mepsevii is 4 mg/kg administered by intravenous infusion every two weeks. Administer the infusion over approximately 4 hours. Infuse the first 2.5% of the total volume over the first hour. After the first hour, increase the infusion rate as tolerated in order to complete infusion over the following 3 hours according to the recommended rate guidelines.

Clinical Results

FDA Approval

The safety and efficacy of Mepsevii were established in clinical trial and expanded access protocols enrolling a total of 23 patients ranging from 5 months to 25 years of age. Patients received treatment with Mepsevii at doses up to 4 mg/kg once every two weeks for up to 164 weeks. Efficacy was primarily assessed via the six-minute walk test in ten patients who could perform the test. After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters. Additional follow-up for up to 120 weeks suggested continued improvement in three patients and stabilization in the others. Two patients in the Mepsevii development program experienced marked improvement in pulmonary function.

Side Effects

Adverse effects associated with the use of Mepsevii may include, but are not limited to, the following:

infusion site extravasation

diarrhea

rash

anaphylaxis

infusion site swelling

peripheral swelling

pruritus

The Mepsevii drug label comes with the following black box warning:

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.

Mechanism of Action

Mepsevii (vestronidase alfa-vjbk) is a recombinant human lysosomal beta glucuronidase. Mucopolysaccharidosis VII (MPS VII or Sly syndrome) is a lysosomal disorder characterized by the deficiency of GUS that results in GAG accumulation in cells throughout the body leading to multisystem tissue and organ damage. Vestronidase alfa-vjbk is a recombinant form of human GUS and is intended to provide exogenous GUS enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow binding of the enzyme to cell surface receptors, leading to cellular uptake of the enzyme, targeting to lysosomes and subsequent catabolism of accumulated GAGs in affected tissues.