FDA

Avlayah

Approved 24 Mar 2026Powder, For solutionInjection

Indications

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 )

Contraindications

None. None ( 4 )

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.

At a glance

Brand name: Avlayah
Active substance: tividenofusp alfa-eknm
Route: Powder, For solution
Dosage form: Injection
Applicant: Denali Therapeutics Inc.
Status: Prescription
FDA approval: 24 Mar 2026
Application: BLA761485-001
RxCUI: 2740020

Indications

Warnings and precautions

If membranous nephropathy is suspected, conduct diagnostic evaluation and initiate appropriate treatment. ( 5.4 )

5.1Hypersensitivity Reactions Including Anaphylaxis

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%) AVLAYAH-treated patient, aged 0.5 years, experienced moderate anemia (hemoglobin 9.2 g/dL), which was considered serious due to the patient's age. Membranous Nephropathy A case of biopsy-confirmed, steroid-refractory membranous nephropathy with immune complex deposits in the kidney was reported in an AVLAYAH-treated patient.

Avlayah

Indications

Contraindications

Warnings and precautions

5.1Hypersensitivity Reactions Including Anaphylaxis

At a glance

Two medicines in one question?

Avlayah

Indications

Contraindications

Warnings and precautions

5.1Hypersensitivity Reactions Including Anaphylaxis

At a glance

Two medicines in one question?

5.2Infusion-Associated Reactions

5.3Anemia

5.4Membranous Nephropathy

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information