It also causes pruritis and can be both extremely painful and irritating. A potential treatment for the condition, nemolizumab, is being developed by Galderma, who licensed it in 2016 from Chugai Pharmaceutical.
Nemolizumab is a humanised antibody that blocks the alpha subunit of the interleukin-31 (IL-31) receptor and is designed to downregulate key pathways in the disease’s pathogenesis.1
IL-31 is a neurocytokine that stimulates the sensory neurons involved in pruritis, contributing to inflammation, dysfunction and remodelling of the skin barrier.
The antibody could also potentially counteract the itch associated with atopic dermatitis.
In a randomised, double-blind Phase II trial, 70 patients with moderate to severe prurigo nodularis were given subcutaneous doses (0.5 mg/kg) of the antibody or a placebo at baseline, week 4 and week 8.2
The initial pruritis score on a scale of 0 to 10 was 8.4 in each group; at week 4, those given the antibody reduced from baseline by 4.5 points (and 1.7 points with the placebo).
Side-effects with the antibody included abdominal pain, diarrhoea and musculoskeletal symptoms. A double-blind, multicentre, randomised Phase III trial has also been done.
In total, 274 patients with prurigo nodularis were given 30 or 60 mg doses, depending on baseline weight, or a placebo, every 4 weeks for 16 weeks.3
Primary endpoints were a reduction of at least four points on the Peak Pruritis Numerical Rating Scale (PP-NRS) and a reduction from baseline in the Investigator’s Global Assessment response of at least two points.
Efficacy was exhibited in both primary endpoints at week 16, with 56% given the antibody having a PP-NRS itch response, compared with 21% with the placebo.
More had an IGA response, too, with 38% of those given the antibody responding and 11% of those on the placebo. The most common adverse events were headache and atopic dermatitis.
Additional secondary endpoints have also been reported.4 At baseline, 63% of treated patients and 70% of the placebo group reported disease-associated pain every day; and, after 16 weeks, 19% of treated patients still reported daily pain, as did 54% of those given the placebo.
The treatment group also reported a higher reduction in the pain’s intensity, along with lower disease severity.
References
- E. Serra-Baldrich, et al., Actas Dermo-Sifiliogr. 113, 674 (2022).
- S. Ständer, et al., N. Engl. J. Med. 382, 702 (2020).
- S.G. Kwatra, et al., N. Engl. J. Med. 389, 1579 (2023).
- A. Reich, et al., European Academy of Dermatology and Venereology Congress 2023 (11–14 October, Berlin, Germany), Abstr. 4147.
