Overview
11 DESCRIPTION Tividenofusp alfa-eknm is a fusion protein consisting of the hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme iduronate-2-sulfatase (IDS) fused to the N-terminus of an immunoglobulin G1 (IgG1) fragment, crystallizable (Fc). It is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Hunter syndrome is an inherited X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS), a lysosomal enzyme, that degrades heparan sulfate (HS) and dermatan sulfate (DS), the two primary glycosominoglycans (GAGs) in the lysosome. Insufficiency or absence of IDS leads to accumulation of GAGs, including HS and DS, and subsequent lysosome dysfunction in multiple organs and tissues, including the central nervous system (CNS). Tividenofusp alfa-eknm provides an exogenous source of IDS.
Indications
- 1 INDICATIONS AND USAGE AVLAYAH is indicated for the treatment of neurologic manifestations of Hunter syndrome (Mucopolysaccharidosis type II, MPS II) when initiated in presymptomatic or symptomatic pediatric patients weighing at least 5 kg prior to advanced neurologic impairment. This indication is approved under accelerated approval based on the reduction of cerebrospinal fluid heparan sulfate [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Common Doses
- 15 mg
- 3 mg
- 7.5 mg
- 5.2 mL
Dosage
2 DOSAGE AND ADMINISTRATION Administration of AVLAYAH should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. (2.1) Obtain a baseline hemoglobin value in all patients. ( 2.1 ) Recommended AVLAYAH maintenance dosage for pediatric patients who weigh at least 5 kg is 15 mg/kg administered once weekly as an intravenous infusion over approximately 4 hours. ( 2.2 , 2.6 ) Initiate AVLAYAH treatment with a dose escalation regimen. ( 2.
Black Box Warning
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies, including AVLAYAH, have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate AVLAYAH in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion-Associated Reactions [see Warnings and Precautions (5.2) ] Anemia [see Warnings and Precautions (5.3) ] Membranous Nephropathy [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥20%) were IAR, upper respiratory tract infection, ear infection, pyrexia, anemia, cough, vomiting, diarrhea, rash, COVID-19, rhinorrhea, nasal congestion, fall, headache, skin...
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.