Regulatory Decision Summary for Nemluvio

This New Drug Submission (NDS) New Active Substance (NAS) was filed to obtain market authorization for Nemluvio (nemolizumab injection) for: i) the treatment of adult and adolescent patients with moderate-to-severe atopic dermatitis (AD); and ii) the treatment of adult patients with moderate-to-severe prurigo nodularis (PN). In both cases, the indication has been restricted to patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable, based on the study populations enrolled in the clinical trials.

The atopic dermatitis (AD) clinical development programme was primarily based on two identical phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicentre studies (ARCADIA 1 and ACADIA 2). The studies primarily consisted of a 16-week initial treatment period where 30 mg nemolizumab or placebo was administered every 4 weeks. This was followed by a 32-week maintenance treatment period (week 16 to week 48) where patients received either 30 mg nemolizumab administered every 4 weeks, 30 mg administered every 8 weeks, or placebo.

In both studies including a total of 1,728 patients, Nemluvio reduced the extent and severity of AD by improving the appearance of the skin (i.e., no/limited eczematous lesions) as measured by the Investigator Global Assessment (IGA) success (0 or 1) and Eczema Area and Severity Index (EASI)-75 (EASI-75: ≥75% improvement in EASI from baseline). The difference in treatment benefit between Nemluvio and placebo demonstrated through the analysis of these two clinical endpoints at Week 16 was both statistically significant and clinically meaningful. The results in both studies for the key secondary endpoints were supportive in demonstrating treatment benefit. The treatment response in favour of Nemluvio relative to placebo observed in the adolescent (≥12 to 18 years of age) subpopulation was consistent with overall population. The treatment effect across different subgroups analysed were generally consistent.

The prurigo nodularis (PN) clinical development programme was primarily based on two identical phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicentre studies (OLYMPIA 2 and 1). The studies primarily consisted of a 16-week (OLYMPIA 2) or 24-week (OLYMPIA 1) treatment period; however, primary efficacy analysis was at 16-weeks in both studies. Subjects weighing <90 kg at baseline received either 30 mg nemolizumab (with 60 mg loading dose at baseline) or placebo every four weeks administered by subcutaneous injection. Subjects weighing ≥90 kg at baseline received either 60 mg nemolizumab or placebo every four weeks.

In both studies including a total of 560 patients, Nemluvio reduced the intense itch characteristic of PN, as measured by Pruritus Numerical Rating Scale, and the extent and severity of PN by improving the appearance of the skin (i.e., no/limited eczematous lesions) as measured by IGA success. The difference in treatment benefit between Nemluvio and placebo demonstrated through the analysis of these two clinical endpoints at Week 16 was both statistically significant and clinically meaningful. Additional key secondary endpoints generally favoured nemolizumab compared to placebo and were supportive of treatment benefit. The treatment effect across different subgroups analysed were generally consistent.

The safety of Nemluvio was primarily characterised in two pivotal Phase 3 studies in patients with prurigo nodularis and two additional pivotal Phase 3 studies in patients with atopic dermatitis. The most common adverse reactions in patients with prurigo nodularis were headache, dermatitis atopic, eczema, eczema nummular, and skin, mucosal, and nail fungal infections. The most common adverse reactions in patients with atopic dermatitis were injection site reactions and hypersensitivity reactions. The rate of serious adverse events was low and there were no deaths considered related to nemolizumab. The risks are adequately described in the product monograph with appropriate risk mitigation strategies. The risks associated with Nemluvio treatment for prurigo nodularis (PN) and atopic dermatitis (AD) will be monitored by routine pharmacovigilance activities.

Overall, based on the data and information evaluated as part of this assessment, the benefit-risk profile was favourable for Nemluvio (nemolizumab) for the authorized indications for the treatment of adult and adolescents with moderate-to-severe atopic dermatitis, and for the treatment of adults with moderate-to-severe prurigo nodularis, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. This applies when Nemluvio is used under the conditions of use recommended in the approved Product Monograph; therefore, a Notice of Compliance (NOC) is recommended.

The risk management plan (RMP) for Nemluvio (nemolizumab) was reviewed by the Marketed Health Products Directorate (MHPD) of Health Canada, and considered acceptable.

The chemistry and manufacturing information submitted for Nemluvio has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The labelling material submitted met all applicable regulations and guidance.

For further details about Nemluvio, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.