What is nemolizumab?
Nemolizumab is a biological therapy used to treat moderate to severe prurigo nodularis (also called nodular prurigo) and atopic dermatitis.
Nemolizumab received its first approval in Japan in 2022 (Mitchga®) for those aged 13 years and over to treat severe atopic dermatitis.
In 2019, the U.S. Food and Drug Administration (FDA) awarded Galderma with a Breakthrough Therapy designation to investigate nemolizumab in treating pruritus associated with prurigo nodularis. Studies on efficacy and safety are currently underway.
Nemolizumab is a monoclonal antibody that acts as an interleukin 31 (IL-31) antagonist. Clinical trials have shown that nemolizumab effectively disrupts the itch-scratch cycle in chronic pruritic skin conditions.
How does nemolizumab work?
- Nemolizumab is a human monoclonal antibody that reduces itching, inflammation, and epithelial remodeling.
- Nemolizumab inhibits the activation of the interleukin 31 (IL-31) receptor, a protein implicated in chronic pruritic skin conditions such as prurigo nodularis. Specifically, nemolizumab blocks IL-31 receptor activation by binding to the alpha subunit of the receptor.
- IL-31 is a cytokine involved in systemic inflammatory and immunoregulatory actions such as itching, impaired skin barrier function, and inflammation. A diverse range of epithelial, neuronal, and immune cells express IL-31 receptors.
- A phase II trial of nemolizumab for prurigo nodularis demonstrated that its therapeutic effect contributed to downregulation of IL-31 responses and normalisation of epithelial markers, leading to decreased pruritus and an increase in healed lesions.
What is nemolizumab used for?
- Approved in Japan in 2022 for use in patients >13 years old with atopic dermatitis not controlled on existing treatments (Mitchga®).
- Clinical trials are underway regarding its use for moderate to severe prurigo nodularis.
- A recent trial evaluated nemolizumab for uraemic pruritus in haemodialysis patients.
Dosage and administration
Nemolizumab is administered as a subcutaneous injection.
The dose approved in Japan for atopic dermatitis treatment is 60mg subcutaneous injection administered at intervals of four weeks.
Benefits of nemolizumab
- Results from a phase II trial (Silverberg et al, 2020) showed nemolizumab 30 mg administered every four weeks (with concurrent topical corticosteroid use) was more effective at reducing Eczema Area and Severity Index (EASI) score compared to placebo after 24 weeks (-68.8% vs -52.1%, p = 0.016). Significant differences between the groups were observed after 8 weeks of treatment.
- A phase III trial (Kabashima et al, 2020) revealed significant efficacy of nemolizumab 60 mg every four weeks (with concomitant topical agents) after 16 weeks compared to placebo in reducing pruritus using visual analogue scale (-42.8% vs -21.4%) and in EASI score (-45.9% vs -33.2%).
- A phase II trial (Ständer et al, 2020) of 70 patients with moderate to severe prurigo nodularis and severe pruritus demonstrated significant reduction in peak pruritus score (-53.0%) at four weeks after one injection of nemolizumab (0.5mg/kg) compared to the placebo control group.
- At four weeks, 24% of patients in the nemolizumab group were found to have 75% or more healed lesions (from baseline), compared to 11% in the control group.
- At twelve weeks, the mean reduction in lesion count was greater in the treatment group compared to placebo (least-squares mean, -12.6 vs -6.1 lesions; difference, -6.5 lesions; unadjusted 95% confidence interval -12.5 to -0.6).
Use in specific populations
Use in paediatric patients for atopic dermatitis
In an open-label phase II clinical trial (Sidbury et al, 2022), 20 adolescent patients (mean age 14.8 years) with moderate to severe atopic dermatitis received a loading dose of 60 mg nemolizumab and a maintenance dose of 30 mg four weekly for 12 weeks, along with background use of topical corticosteroids or topical calcineurin inhibitors.
- From baseline to week 16: reduction of 43.2% (+/-37%) observed in peak pruritus numeric rating scale, and reduction of 66.5% (+/-32.5%) in Eczema Area and Severity Index.
- Pharmacokinetics: linear elimination, first-order absorption, and mean half-life of 16.7 days.
- Six patients experienced adverse events, and 3/20 discontinued early as a result. Adverse events included:
- Eczemoid dermatitis
- Peripheral oedema (unilateral and bilateral)
- Staphylococcal skin infection.
- No deaths were reported.
Use in uraemic pruritus secondary to chronic kidney disease
Patients with chronic kidney disease may experience severe uraemic pruritus. The pathogenesis of uraemic pruritus is unknown, but interleukin 31 (IL-31) is suspected to be involved.
A phase II trial (Kinugasa et al, 2021) investigated the efficacy and safety of nemolizumab in treating uraemic pruritus in hemodialysis patients. Patients received a one-time subcutaneous injection of nemolizumab (0.125, 0.5, or 2.0 mg/kg), control, or nalfurafine hydrochloride (NAL).
- In this study, there was not a significant difference in pruritus assessed using a visual analogue scale (VAS) at four weeks between the nemolizumab and placebo groups.
- Rates of treatment-related adverse events in the nemolizumab groups (69.2–73.3%) were similar to the NAL (76.9%) and placebo groups (85.7%).
- In the nemolizumab groups, reported adverse effects included:
- Renal anaemia
- Among all groups, no deaths were recorded.
What are the adverse effects of nemolizumab?
Nemolizumab generally had a good safety and tolerability profile compared to control or placebo groups. A 64-week extension study found no new safety concerns.
Adverse events reported in clinical trials include:
- Gastrointestinal symptoms (eg, abdominal pain, diarrhoea)
- Musculoskeletal symptoms (eg, arthralgia, muscle spasms, jaw pain)
- Upper respiratory tract infection
- Exacerbation of atopic dermatitis (in patients with pre-existing atopic dermatitis), resulting in 10/264 patients discontinuing the 64-week nemolizumab extension study
- Abnormal creatine phosphokinase levels
- Injection site reactions.
Serious adverse events that occurred in patients taking nemolizumab in clinical trials accounted for less than 5% of reported adverse events, and included:
- Psoriasiform rash
- Clavicular fracture
- Bladder lithiasis
- Meniere’s disease
- Peripheral oedema
- Staphylococcal skin infection
- Exacerbation of atopic dermatitis.
Ongoing phase III trials will further explore the safety and efficacy of nemolizumab in treating prurigo nodularis and atopic dermatitis.
Currently, there are no formal drug interaction studies associated with nemolizumab.
See also immunisation in immunosuppressed dermatology patients for information on vaccination.
What are the contraindications with nemolizumab?
- Hypersensitivity to nemolizumab or any of its constituents.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).