Tividenofusp alfa

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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Limitations of Use AVLAYAH is not recommended for use in combination with other enzyme replacement therapies for the treatment of Hunter syndrome.

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. The fragment, crystallizable (Fc) component of tividenofusp alfa-eknm binds to the apical domain of the transferrin receptor (TfR) and delivers IDS to peripheral tissues and to the CNS through receptor-mediated transcytosis across the blood-brain barrier.

Administration of AVLAYAH should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Obtain a baseline hemoglobin value in all patients. 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. Initiate AVLAYAH treatment with a dose escalation regimen. See the full prescribing information for dosage and administration modifications and monitoring. See the full prescribing information for preparation and administration instructions.

None. None

Boxed 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. Infusion-Associated Reactions (IARs): If a severe IAR occurs, discontinue AVLAYAH and initiate appropriate medical treatment. Anemia: Obtain baseline hemoglobin levels in all patients and monitor 3 months after initiation, and as clinically indicated. Administer appropriate supportive measures for anemia based on clinical judgment. Membranous Nephropathy: Monitor serum creatinine and urinary protein to creatinine ratio. If membranous nephropathy is suspected, conduct diagnostic evaluation and initiate appropriate treatment.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis Infusion-Associated Reactions Anemia Membranous Nephropathy 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 abrasion, and urticaria.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.