Nemolizumab (Monograph)

Brand name: Nemluvio
Drug class: Immunomodulatory Agents

Introduction

Recombinant humanized immunoglobulin G₂ (IgG₂) monoclonal antibody; interleukin-31 (IL-31) receptor antagonist.

Uses for Nemolizumab

Atopic Dermatitis

Treatment of moderate-to-severe atopic dermatitis, in combination with topical corticosteroids and/or topical calcineurin inhibitors, in adults and pediatric patients ≥12 years of age who have had an inadequate response to topical prescription therapy.

Guidelines from the American Academy of Dermatology (AAD) and other experts recommend the use of emollients/moisturizers, topical corticosteroids, and topical calcineurin inhibitors for management of atopic dermatitis; systemic options such as biologics (e.g., dupilumab, tralokinumab) and Janus kinase (JAK) inhibitors may be considered for advanced disease, but systemic corticosteroids generally not recommended. Specific recommendations for use of nemolizumab not yet provided in these guidelines.

Prurigo Nodularis

Treatment of adults with prurigo nodularis.

Management of prurigo nodularis includes topical therapies, neuromodulating agents, and targeted biologics such as dupilumab and nemolizumab; treatment should be individualized based on disease severity and patient needs.

Nemolizumab Dosage and Administration

General

Pretreatment Screening

Complete age-appropriate vaccinations per current immunization guidelines before starting therapy with nemolizumab-ilto. Avoid use of live vaccines during treatment.

Administration

Sub-Q Administration

Administer by sub-Q injection only.

Available as a single-dose prefilled pen with a dual chamber containing 30 mg of lyophilized powder in one chamber and water for injection in the other chamber.

Reconstitute the drug prior to administration by activating the pen to mix the contents of the 2 chambers.

Reconstitution

Prior to reconstitution, remove carton from refrigerator for approximately 30-45 minutes to allow the drug to reach room temperature.

Inspect the dual chamber pen; do not use if powder is not white or diluent is cloudy.

Reconstitute the pen according to the manufacturer's instructions for use. Ensure that the solution is clear; use within 4 hours and discard unused portions. Consult the manufacturer's labeling for additional details on activation of the prefilled pen.

Sub-Q Administration

Use nemolizumab-ilto under guidance of healthcare provider.

Train patients and caregivers in preparation and administration before self-injection.

In pediatric patients ≥12 years of age receiving the drug for atopic dermatitis, administer by or under supervision of a trained adult or caregiver.

Administer the initial dose as two injections at separate sites.

Inject sub-Q into thighs or abdomen, avoiding the 2 inch area around the navel; upper arm injections require a caregiver or healthcare provider.

Rotate sites with each injection, and avoid injecting into tender, inflamed, swollen, damaged, bruised, or scarred skin.

Dosage

Pediatric Patients

Atopic Dermatitis

Sub-Q

Pediatric patients ≥12 years of age: Initially, 60 mg (two 30-mg injections) followed by 30 mg every 4 weeks. After 16 weeks, for patients achieving clear or almost clear skin, recommended dosage is 30 mg every 8 weeks.

Use concomitantly with topical corticosteroids and/or topical calcineurin inhibitors. Discontinue topical therapies once the disease has sufficiently improved.

If a dose is missed, administer as soon as possible, and then resume regular dosing schedule.

Adults

Atopic Dermatitis

Sub-Q

Initially, 60 mg (two 30 mg injections) followed by 30 mg every 4 weeks. After 16 weeks, for patients achieving clear or almost clear skin, recommended dosage is 30 mg every 8 weeks.

Use concomitantly with topical corticosteroids and/or topical calcineurin inhibitors. Discontinue topical therapies once the disease has sufficiently improved.

If a dose is missed, administer as soon as possible, and then resume regular dosing schedule.

Prurigo Nodularis

Sub-Q

<90 kg: 60 mg (two 30 mg sub-Q injections) initially, then 30 mg every 4 weeks.

≥90 kg: 60 mg sub-Q initially, then 60 mg every 4 weeks.

If a dose is missed, administer the missed dose as soon as possible, and then resume regular dosing schedule.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No dosage adjustments needed.

Cautions for Nemolizumab

Contraindications

Known hypersensitivity to nemolizumab-ilto or any excipients in the formulation.

Warnings/Precautions

Hypersensitivity

Hypersensitivity reactions (e.g., facial edema) reported. Discontinue nemolizumab-ilto and institute appropriate therapy if clinically significant hypersensitivity reaction occurs.

Vaccinations

Complete age-appropriate vaccines before starting nemolizumab-ilto. Avoid live vaccines during treatment.

Immunogenicity

Anti-drug antibodies and neutralizing antibodies detected. Antibodies were associated with reduced drug concentrations in some patients with atopic dermatitis; however, no clinically important effects on safety or efficacy observed over treatment duration studied.

Specific Populations

Pregnancy

Insufficient data to determine risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Crosses placenta, peaking in the third trimester, and may affect an infant’s immune response. Delay live vaccines for at least 3 months after birth.

Lactation

No data on the presence of nemolizumab in human milk or whether the drug has any effects on a breastfed child or on milk production. Consider the benefits of breastfeeding, mother’s need for nemolizumab, and any potential risks to the infant from the drug or maternal condition.

Pediatric Use

Atopic dermatitis: Safety and efficacy established in pediatric patients ≥12 years of age with moderate to severe atopic dermatitis.

Prurigo nodularis: Safety and efficacy not established.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine if they respond differently than younger patients.

Hepatic Impairment

No significant pharmacokinetic differences in mild to moderate hepatic impairment; effects in severe impairment are unknown.

Renal Impairment

No significant pharmacokinetic differences in mild to moderate renal impairment; effects in severe impairment are unknown.

Common Adverse Effects

Atopic dermatitis: Most common adverse reactions (≥1%) were headache (including migraine), arthralgia, urticaria, myalgia.

Prurigo nodularis: Most common adverse reactions (≥1%) were headache, dermatitis atopic, eczema, eczema nummular.

Drug Interactions

Effects of drug interactions may vary based on underlying disease.

In patients with atopic dermatitis, no clinically significant impact of nemolizumab on pharmacokinetics of the following CYP substrates observed: midazolam (a CYP3A4/5 substrate), warfarin (a CYP2C9 substrate), omeprazole (a CYP2C19 substrate), metoprolol (a CYP2D6 substrate), and caffeine (a CYP1A2 substrate).

In patients with prurigo nodularis, nemolizumab may modulate cytokine levels, affecting CYP activity. Monitor and adjust dosages of CYP substrates with narrow therapeutic indices (e.g., warfarin, cyclosporine) as needed when initiating or discontinuing nemolizumab.

Vaccines

Not known whether nemolizumab can affect safety or effectiveness of live vaccines; avoid use of live vaccines during treatment with nemolizumab.

Nemolizumab Pharmacokinetics

Absorption

Bioavailability

Exposure is approximately dose-proportional up to 30 mg, with bioavailability decreasing by 9% at a dose of 60 mg and by 15% at a dose of 90 mg.

Plasma Concentration

Peak plasma concentrations achieved within approximately 6 days after 60-mg dose.

Steady-state concentrations in patients with prurigo nodularis achieved by 4 weeks in patients <90 kg and by 12 weeks in patients ≥90 kg.

Special Populations

Exposure decreases with increasing body weight. Not expected to have a clinically important effect in patients with atopic dermatitis; however, may impact skin lesion response in patients with prurigo nodularis, necessitating weight-based dosing.

Age, renal impairment, and hepatic impairment do not appear to have clinically important effects on the pharmacokinetics of nemolizumab.

Distribution

Half-life

Terminal half-life is approximately 18.9 days.

Elimination

Metabolism

Metabolic pathway not characterized but expected to be degraded into small peptides via catabolic pathways.

Stability

Storage

Parenteral

Prefilled pen

Store in refrigerator at 2-8°C in original carton to protect from light.

Do not freeze or expose to heat or direct sunlight.

May be stored at room temperature (up to 25°C) for a single period of up to 90 days. Record date when removed from refrigerator; do not use beyond expiration date or 90 days after removal, whichever comes first.

Actions

Recombinant humanized monoclonal IgG₂ antibody; interleukin-31 receptor alpha (IL-31RA) antagonist.
Blocks IL-31 signaling by binding to IL-31RA, a naturally occurring cytokine involved in itching, inflammation, epidermal dysregulation, and fibrosis.
Inhibits IL-31 induced responses, including the release of proinflammatory cytokines and chemokines.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Advise patients to discontinue nemolizumab and seek immediate medical attention if they experience symptoms of a hypersensitivity reaction.
Instruct patients to inform their healthcare provider that they are taking nemolizumab before receiving any vaccination.
Instruct patients and/or caregivers to receive proper training in sub-Q injection technique prior to self-injection. Inform patients and/or caregivers that Galderma Customer Support may be called toll-free for assistance at 1-866-735-4137.
Inform patients and/or caregivers of proper pen disposal and caution against any reuse of needles. Instruct patients and/or caregivers to discard used pens in an appropriate Sharps disposal container following safe needle disposal practices.
Advise patients/caregivers of the importance of complying with the dosing schedule. If a dose is missed, instruct patients and/or caregivers to administer the injection as soon as possible, and thereafter, resume dosing at the regular scheduled time.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nemolizumab-ilto is available through designated specialty pharmacies. Contact manufacturer or consult the nemolizumab-ilto website ([Web]) for specific availability information.