AVLAYAH tividenofusp alfa-eknm 150 mg/5mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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7.5 mg / 5 mL
UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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3 mg / 5 mL
UNII 7T1F30V5YH
A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
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14.6 mg / 5 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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9.5 mg / 5 mL
UNII 70WT22SF4B
A mineral salt that acts as a buffer to maintain the pH balance of the medication. It helps stabilize the drug's potency and prevents unwanted chemical changes during storage.
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8.9 mg / 5 mL
UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
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300 mg / 5 mL
UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
7 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Avlayah 150 mg/5mLthis 84976-0001-01 | Denali | 1 vial | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 84976-0001-01 You're viewing this | 1 VIAL in 1 CARTON (84976-001-01) / 5 mL in 1 VIAL | 2026-04-06 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed 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., anaphylaxis) occurs, discontinue AVLAYAH and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ] . WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning.
Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. ( 5.1 ) Initiate AVLAYAH in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. ( 5.1 ) If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue AVLAYAH and immediately initiate appropriate medical treatment, including use of epinephrine.
( 5.1 )
🎯 Indications and Usage ▾
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).
Limitations of Use AVLAYAH is not recommended for use in combination with other enzyme replacement therapies for the treatment of Hunter syndrome. AVLAYAH is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme 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. ( 1 ) This indication is approved under accelerated approval based on reduction of cerebrospinal fluid heparan sulfate observed in patients treated with AVLAYAH.
Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). ( 1 ) Limitations of Use AVLAYAH is not recommended for use in combination with other enzyme replacement therapies. ( 1 )
⏱️ Dosage and Administration ▾
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. ( 2.2 ) See the full prescribing information for dosage and administration modifications and monitoring. ( 2.3 ) See the full prescribing information for preparation and administration instructions.
( 2.4 , 2.6 )
2.1Important Recommendations Prior to AVLAYAH Treatment Initiation Administer AVLAYAH under the supervision of a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1) ] . Initiate AVLAYAH in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ]. Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1 , 5.2) ] .
Obtain a baseline hemoglobin value in all patients [see Warnings and Precautions (5.3) ] .
2.2Recommended Dosage The recommended starting dosage of AVLAYAH for pediatric patients weighing at least 5 kg is 3 mg/kg administered once weekly via intravenous infusion. To reduce the risk of infusion-associated reactions (IARs), follow the dose escalation regimen in Table 1 [see Warnings and Precautions (5.2) ] . Administer each dosage level for at least 4 weeks before escalating to the next dosage level.
The recommended maintenance dosage of AVLAYAH for pediatric patients who weigh at least 5 kg is 15 mg/kg administered once weekly via intravenous infusion. Table 1: Recommended AVLAYAH Dosage for Pediatric Patients Weighing ≥5 kg a Dosing Week Dosage Level a Do not escalate the dosage level if the current dosage level is not tolerated [see Dosage and Administration (2.3) ] . Week 1 to Week 4 3 mg/kg once weekly Week 5 to Week 8 7.5 mg/kg once weekly Week 9 and beyond 15 mg/kg once weekly (maintenance dosage)
2.3Dosage and Administration Modifications and Monitoring In the event of a severe hypersensitivity reaction (e.g., anaphylaxis) or a severe IAR, discontinue AVLAYAH and immediately initiate appropriate medical treatment. Consider the risks and benefits of re-administering AVLAYAH following a severe reaction. If the decision is made to re-administer AVLAYAH, re-evaluate pre-treatment medications, slow the infusion rate, and/or reduce the AVLAYAH dose.
Monitor patients closely upon re-administration of AVLAYAH [see Warnings and Precautions (5.1 , 5.2) ] . In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, temporarily hold the infusion and/or reduce the infusion rate by at least 50% from the current rate, then titrate up to the recommended infusion rate as tolerated (see Table 3 ) [see Warnings and Precautions (5.1 , 5.2) ]. If the dose has been decreased due to an adverse reaction, evaluate when it is appropriate to increase the dose and follow the recommended dose escalation regimen to achieve the maintenance dosage of 15 mg/kg once weekly [see Dosage and Administration (2.2) ].
2.4Preparation Instructions Prepare AVLAYAH using polypropylene syringes and infusion bags composed of polyvinylchloride (PVC) or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP); infusion sets composed of PVC or PE; and filter membranes composed of polyethersulfone (PES). Use aseptic technique during preparation. Reconstitute and dilute AVLAYAH in the following manner: Reconstitution Instructions 1) Determine the number of AVLAYAH vials to be reconstituted based on the patient's weight in kg and the recommended dosage [see Do…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For injection: 150 mg of tividenofusp alfa-eknm as a white to off-white lyophilized powder with a cake-like appearance in a single-dose vial for reconstitution and further dilution. For injection: 150 mg of tividenofusp alfa-eknm as a lyophilized powder in a single-dose vial for reconstitution and further dilution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Infusion-Associated Reactions (IARs) : If a severe IAR occurs, discontinue AVLAYAH and initiate appropriate medical treatment. ( 5.2 ) 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.
( 5.3 ) Membranous Nephropathy: Monitor serum creatinine and urinary protein to creatinine ratio. If membranous nephropathy is suspected, conduct diagnostic evaluation and initiate appropriate treatment. ( 5.4 )
5.1Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with enzyme replacement therapies (ERTs), including AVLAYAH [see Adverse Reactions (6) ] . Symptoms of anaphylaxis that have occurred with AVLAYAH have included tachycardia, hypotension, wheezing, vomiting, hives, and lip and tongue swelling. Anaphylaxis has occurred during the early course of ERT and after extended duration of therapy.
Administer AVLAYAH under the supervision of a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Initiate AVLAYAH in a healthcare setting with appropriate medical monitoring and support measures including access to cardiopulmonary resuscitation equipment. Prior to AVLAYAH administration, consider pre-treatment with antihistamines, antipyretics, and/or corticosteroids.
If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue AVLAYAH and immediately initiate appropriate medical treatment, including use of epinephrine. Consider the risks and benefits of re-administering AVLAYAH following a severe hypersensitivity reaction (including anaphylaxis). If the decision is made to re-administer AVLAYAH, re-evaluate pre-treatment medications (e.g., antihistamines, antipyretics, and/or corticosteroids), slow the infusion rate, and/or reduce the AVLAYAH dose.
Monitor patients closely upon re-administration of AVLAYAH. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and to seek immediate medical care should symptoms occur. If a mild or moderate hypersensitivity reaction occurs, temporarily hold the infusion and/or reduce the infusion rate by at least 50% from the current rate, then titrate up to the recommended infusion rate as tolerated (see Table 3 ).
Re-evaluate the pre-treatment medication regimen [see Dosage and Administration (2.3) ] . If the dose has been decreased due to an adverse reaction, evaluate when it is appropriate to increase the dose and follow the recommended dose escalation regimen to achieve the maintenance dosage of 15 mg/kg once weekly [see Dosage and Administration (2.2) ].
5.2Infusion-Associated Reactions Infusion-associated reactions (IARs) have been reported in patients treated with AVLAYAH [see Adverse Reactions (6.1) ] . IARs are defined as adverse reactions occurring during or within 24 hours of the infusion. Symptoms of IARs observed with AVLAYAH can include (but are not limited to) chills, angioedema, hypotension, tachycardia, urticaria, vomiting, wheezing, pyrexia, flushing, erythema, rash, cough, diarrhea, abdominal pain, retching, headache, irritability, and papules.
IARs have been reported more frequently in ERT-naïve patients compared to ERT-experienced patients. Cases of infusion-associated reactions occurring 2 hours or more after completion of the infusion have occurred with AVLAYAH. Prior to AVLAYAH administration, consider pre-treatment with antihistamines, antipyretics, and/or corticosteroids to reduce the risk of IARs.
IARs may still occur in patients after receiving pre-treatment. Onset of IARs was most common during the first 8 weeks of treatment with a median time to onset of approximately 2 weeks for the first IAR; IARs declined in frequency with continued use of AVLAYAH. IARs may still occur despite…
🤒 Adverse Reactions ▾
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 abrasion, and urticaria.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Denali Therapeutics toll-free at 1-833-ONE-DNLI (1-833-663-3654) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of AVLAYAH was evaluated in male pediatric patients with Hunter syndrome in Trial 1 [see Clinical Studies (14) ] . A total of 47 male patients (age range: 3 months to 13 years) received intravenous AVLAYAH at 3 mg/kg to 30 mg/kg (0.2 to 2 times the approved recommended maintenance dose) weekly, and the majority of patients received 15 mg/kg intravenously weekly after Week 24.
The median (minimum, maximum) duration of exposure was 117 (19, 219) weeks. In Trial 1, the most common adverse reactions (≥20%) reported in AVLAYAH-treated patients were infusion-associated reaction (IAR), upper respiratory tract infection, ear infection, pyrexia, anemia, cough, vomiting, diarrhea, rash, COVID-19, rhinorrhea, nasal congestion, fall, headache, skin abrasion, and urticaria. Dose interruptions of AVLAYAH due to an adverse reaction occurred in 91% of patients.
The most frequently reported adverse reaction leading to dose interruption was IAR (31 [66%] patients). Other frequently reported adverse reactions leading to dose interruption were COVID-19 (18 [38%] patients), pyrexia (16 [34%]), upper respiratory tract infection (16 [34%]), nasal congestion (6 [13%]), and vomiting (6 [13%]). Dose interruption included skipped infusions due to an adverse reaction as well as temporary infusion pauses with subsequent completion during the same visit.
Dose reductions of AVLAYAH due to adverse reactions occurred in 57% of patients; the majority of these reactions were IARs. In Trial 1, one (2%) AVLAYAH-treated patient experienced anaphylaxis, which occurred in the first month of treatment. Table 4 summarizes adverse reactions that occurred in >15% of AVLAYAH-treated pediatric patients with Hunter syndrome.
Table 4: Adverse Reactions That Occurred in >15% in AVLAYAH-treated Pediatric Patients With Hunter Syndrome (Trial 1) Adverse Reaction Any Severity N (%) (N = 47) a Infusion-associated reaction includes infusion-related reaction. b Ear infection includes ear infection, otitis media, otitis media acute, otitis externa. c Anemia includes anemia, iron deficiency anemia, and decreased hemoglobin. Infusion-associated reaction a 41 (87%) Upper respiratory tract infection 28 (60%) Ear infection b 26 (55%) Pyrexia 26 (55%) Anemia c 24 (51%) Cough 22 (47%) Vomiting 20 (43%) Diarrhea 19 (40%) Rash 19 (40%) COVID-19 18 (38%) Rhinorrhea 18 (38%) Nasal congestion 17 (36%) Fall 11 (23%) Headache 11 (23%) Skin abrasion 11 (23%) Urticaria 10 (21%) Constipation 8 (17%) Contusion 8 (17%) Gastroenteritis 8 (17%) Infusion site extravasation 8 (17%) Insomnia 8 (17%) Neutropenia 8 (17%) Description of Selected Adverse Reactions Infusion-Associated Reaction Three (6%) AVLAYAH-treated patients experienced severe IARs.
One patient permanently discontinued treatment due to an IAR. Anemia Two (4%) AVLAYAH-treated patients experienced severe anemia (defined as hemoglobin <8 g/dL) prior to Week 24. One (2%…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data on the use of AVLAYAH during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal studies to evaluate the potential for embryofetal developmental toxicity and pre- and postnatal developmental toxicity of tividenofusp alfa-eknm have not been conducted. The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2Lactation Risk Summary There are no data on the presence of tividenofusp alfa-eknm in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AVLAYAH and any potential adverse effects on the breastfed infant from AVLAYAH or from the underlying maternal condition.
8.4Pediatric Use The safety and effectiveness of AVLAYAH have been established under accelerated approval 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 and the information on this use is discussed throughout the labeling [see Indications and Usage (1) ] . The safety and effectiveness of AVLAYAH have not been established in pediatric patients weighing less than 5 kg.
8.5Geriatric Use Clinical trials of AVLAYAH in patients with Hunter syndrome did not include patients 65 years of age or older.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on the use of AVLAYAH during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal studies to evaluate the potential for embryofetal developmental toxicity and pre- and postnatal developmental toxicity of tividenofusp alfa-eknm have not been conducted. The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of AVLAYAH have been established under accelerated approval 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 and the information on this use is discussed throughout the labeling [see Indications and Usage (1) ] . The safety and effectiveness of AVLAYAH have not been established in pediatric patients weighing less than 5 kg.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical trials of AVLAYAH in patients with Hunter syndrome did not include patients 65 years of age or older.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
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. Tividenofusp alfa-eknm is internalized via binding to the mannose-6-phosphate receptor on the cell surface and transported into lysosomes where it is thought to exert enzymatic activity and reduce accumulated GAGs. In addition, since TfR is ubiquitously expressed, it is expected that the interaction of tividenofusp alfa-eknm and TfR will contribute to its uptake into cells in the brain and peripheral tissues.
12.2Pharmacodynamics In clinical studies with AVLAYAH, the relative concentrations of HS or DS in human cerebrospinal fluid (CSF) and urine were estimated based on an assessment of selected disaccharides following enzymatic digestion of HS or DS. It is not possible to directly quantify intact HS or DS concentrations in human CSF or urine using currently available bioanalytical methods. Differences in bioanalytical methods preclude meaningful comparison of the pharmacodynamic results based on HS or DS concentrations in clinical studies with AVLAYAH with the results in other clinical studies.
In Trial 1, reductions in CSF HS from baseline were observed in AVLAYAH-treated pediatric patients with Hunter syndrome [see Clinical Studies (14) ]. Reductions in urine HS (86%), urine DS (91%), and total urine GAGs (57%) from baseline were observed at Week 24 in AVLAYAH-treated pediatric patients with Hunter syndrome. At baseline, 2 of 47 (4%) patients had total urine GAG levels below the upper limit of normal (ULN).
At Week 24, 26 of 38 (68%) patients had total urine GAG levels below the ULN. The relationship between changes in CSF HS, urine HS, urine DS, and total urine GAG levels to clinical response in patients with Hunter syndrome has not been established. In Trial 1, higher serum tividenofusp alfa-eknm concentrations appeared to be associated with greater reductions of CSF HS and urine HS concentrations from baseline, with maximum effect achieved at 15 mg/kg of AVLAYAH once weekly (the recommended maintenance dosage).
The time to maximum effect on pharmacodynamic response and the exposure-response relationship for the safety and effectiveness of tividenofusp alfa-eknm have not been fully characterized.
12.3Pharmacokinetics The pharmacokinetics of tividenofusp alfa-eknm were evaluated in pediatric patients with Hunter syndrome aged 3 months to 13 years (age at baseline). The maximum serum concentration (C max ) increased proportionally with dose, while the area under the serum concentration-time curve (AUC tau ) increased in a greater-than-dose-proportional manner across the dose range of 3 mg/kg to 30 mg/kg (0.2 to 2 times the approved recommended maintenance dosage). Table 5 shows the C max and AUC tau of tividenofusp alfa-eknm following the recommended starting dosage and recommended maintenance dosage [see Dosage and Administration (2.2) ] .
Table 5: C max and AUC tau of Tividenofusp Alfa-eknm in Pediatric Patients With Hunter Syndrome Pharmacokinetic Parameter Week 1 (3 mg/kg weekly) Week 24 (15 mg/kg weekly) Geometric Mean (Range) Geometric Mean (Range) Abbreviations: AUC tau = area under the serum concentration-time curve from 0 to 168 hours after the start of infusion; C max = maximum serum concentra…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
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. Tividenofusp alfa-eknm is internalized via binding to the mannose-6-phosphate receptor on the cell surface and transported into lysosomes where it is thought to exert enzymatic activity and reduce accumulated GAGs. In addition, since TfR is ubiquitously expressed, it is expected that the interaction of tividenofusp alfa-eknm and TfR will contribute to its uptake into cells in the brain and peripheral tissues.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied AVLAYAH (tividenofusp alfa-eknm) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder with a cake-like appearance in a single-dose vial. Each vial contains 150 mg of tividenofusp alfa-eknm. AVLAYAH is available as one carton containing a 150 mg single-dose vial (NDC 84976-001-01).
Storage and Handling 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.
📦 Storage and Handling ▾
Storage and Handling 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.
📋 Description ▾
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. The approximate molecular weight of tividenofusp alfa-eknm is 110 kDa.
AVLAYAH (tividenofusp alfa-eknm) for injection is a sterile, preservative-free, white to off-white lyophilized powder with a cake-like appearance for intravenous infusion after reconstitution and dilution. Each single-dose vial contains 150 mg tividenofusp alfa-eknm, and the inactive ingredients dibasic sodium phosphate (5 mg), methionine (7.5 mg), monobasic sodium phosphate (7.7 mg), polysorbate 20 (3 mg), sodium chloride (14.6 mg), and sucrose (300 mg). The pH is 6.5 after reconstitution.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Hypersensitivity Reactions Including Anaphylaxis, and Infusion-Associated Reactions Advise the patient and/or caregiver that life-threatening hypersensitivity reactions, including anaphylaxis, and infusion-associated reactions (IARs) may occur with AVLAYAH treatment. Advise the patient and/or caregiver that anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Inform the patient and/or caregiver of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and IARs and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1 , 5.2) ] .
Anemia Inform the patient and caregiver that anemia may occur during AVLAYAH treatment. Advise the patient and/or caregiver of the symptoms of anemia (e.g., fatigue, pallor). Instruct the patient and/or caregiver to contact their healthcare provider if those symptoms occur [see Warnings and Precautions (5.3) ] .