IL-31 Drug Succeeds for Prurigo Nodularis

An investigational monoclonal antibody targeting interleukin-31 (IL-31) receptor A improved symptoms of moderate-to-severe prurigo nodularis (PN) in a small randomized trial.

After only 4 weeks, PN patients assigned to subcutaneous nemolizumab in the phase II study had a significant reduction in their pruritus score compared with those on placebo, meeting the trial's primary endpoint, reported Sonja Ständer, MD, of University Hospital Münster in Germany, and colleagues.

Compared to baseline, peak pruritus score on the numerical rating scale dropped by 53%, on average, for the 34 patients on nemolizumab, as compared with a 20% reduction for the 36 individuals on placebo (-32.8% difference, 95% CI -46.8% to -18.8%, P<0.001), the group wrote in the New England Journal of Medicine.

And after 12 weeks, those on nemolizumab had an average 12.6 fewer lesions versus 6.1 fewer with placebo. This held true through the last follow-up visit at week 18 -- 10 weeks after the last dose -- where the average reduction in lesion count was 13.3 and 7.5 in the nemolizumab and placebo groups, respectively.

The researchers expected PN and the associated itch to improve during the trial, Ständer told MedPage Today, which turned out to be true, but she said they were surprised at how quickly skin lesions healed -- with some patients healing within the duration of the study period.

Other than corticosteroids and topical creams, there are currently no approved treatment options for PN, Ständer said, a driving force behind wanting to conduct this trial.

"PN is a very distressing disease," she underscored. "The pharmaceutical development of novel therapies which might receive a label is highly needed."

"Previous studies suggested that interleukin-31 (IL-31) is an important mediator in PN," Ständer continued. "As nemolizumab is an IL-31 antagonist, the hypothesis of this trial was that the substance might have a beneficial influence on itch and the disease itself. Both aims have been achieved in this trial."

The phase II study included 70 adults with moderate-to-severe PN -- 20 or more nodules -- or severe PN, defined as an average daily pruritus score of 7 out of 10 (worst itching imaginable). Individuals with lesions on only one side of the body, chronic pruritus due to another condition, neuropathic or psychogenic pruritus, brachioradial pruritus, delusional parasitosis, or dermatitis artefacta were among the exclusion criteria.

Participants randomized to the study drug were given a total of three subcutaneous injections at baseline, week 4, and week 8 at a dose of 0.5 mg/kg of body weight.

Although adverse event (AEs) rates were similar between the treatment (68%) and placebo (67%) groups, nemolizumab was associated with gastrointestinal events such as abdominal pain and diarrhea, occurring in 21% of recipients. Other common AEs in the treatment group included musculoskeletal or connective-tissue disorders in 18%; injury, poisoning, or procedural complications in 12%; and bronchitis in 6%.

Based on these findings, which were first presented at the 2019 European Academy of Dermatology and Venereology annual congress, the FDA granted nemolizumab breakthrough therapy designation for the treatment of pruritus associated with PN in December of last year. Galderma said they are "actively preparing for the initiation" of a phase III trial of nemolizumab for PN in 2020.

Nemolizumab's benefits also extend to moderate-to-severe atopic dermatitis. In October 2019, Galderma launched a phase III trial testing the drug in moderate-to-severe atopic dermatitis following positive phase IIb data.

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