Study Finds Nemolizumab Significantly Improved Signs, Symptoms in Prurigo Nodularis

Treatment of prurigo nodularis with nemolizumab monotherapy results in clinically meaningful and statistically significant sign and symptom improvements in the skin disease, according to recent findings, confirming the efficacy of targeting interleukin (IL)-31 signaling with nemolizumab.1

Such findings were the conclusion of new research assessing nemolizumab among those with moderate-to-severe prurigo nodularis. The condition is a chronic and pruritic neuroimmunologic skin condition which is known to be severe.

Nemolizumab is an IL-31 receptor alpha antagonist, designed with the aim of down-regulating some of the key pathways in the pathogenesis of this skin condition. The new recent phase 3 analysis evaluating the drug, titled OLYMPIA 1, was authored in part by Sonja Ständer, MD, from the University Hospital Münster’s Center for Chronic Pruritus and department for dermatology.

“Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions,” Ständer and colleagues wrote. “Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2).”1,2

Background and Design

The investigative team’s principal aim was to evaluate both the efficacy of the drug and occurrence of adverse events among adult study participants with moderate-to-severe prurigo nodularis given nemolizumab. They compared these subjects with those receiving a placebo.

Overall, the OLYMPIA 1 study was designed as a phase 3, multicenter, randomized clinical study which the team conducted in the period between August 2020 - March 2023. The analysis was carried out by the investigators across 77 centers found within 10 countries.

Those determined to be participants for OLYMPIA 1 were given random assignment, in a 2:1 ratio, to be treated with either nemolizumab monotherapy or a placebo. Nemolizumab was administered at a dosage of either 30 mg or 60 mg, with the research team providing the drug on an every-4-week basis.

The team administered the drug at 30 or 60 depending on whether subjects’ baseline weights were shown to be below 90 kg or 90 kg and above, respectively. The investigators focused their research on adult participants who were noted as having moderate-to-severe prurigo nodularis.

This condition would be defined by subjects having an Investigator’s Global Assessment (IGA) score of 3 or more, at least 20 nodules, and a Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7.0 or more. The researchers’ work first included a screening phase of up to 4 weeks, followed then by a 24-week phase in which treatment occurred, and then an 8-week period for follow-up meetings.

In terms of primary outcomes, the investigators assessed the disease at the 16-week mark, with focus specifically on 2 endpoints. One was the proportion of participants reporting IGA success, defined as a score of 0 or 1 along with at least a 2-grade improvement from the point of baseline. The second was achieving an itch response, which the team defined as an improvement of 4 points minimum from baseline in weekly average PP-NRS scores.

Significant Findings

The investigators concluded that among the 286 participants, there had been a mean body weight of 85.0 kg, a mean age of 57.5 years, and 58.0% of them had been female. They noted that 190 were given administration of nemolizumab and 96 were assigned to the placebo arm of the study.

Significantly more individuals at the 16-week mark in the nemolizumab arm were shown to have achieved itch response, with 58.4% compared to only 16.7% (95% CI 29.4%-50.8%, P < .001). This was also shown to be the case for IGA success, with 26.3% having such a response versus 7.3% (95% CI 6.7%-22.6%, P = .003).

The investigative team’s ad hoc analysis they conducted at the 24-week mark confirmed their findings, with the team reporting that itch response was seen in 58.3% of those in the nemolizumab cohort as opposed to 20.4% in the placebo cohort (95% CI 27.5%-49.9%). Additionally, the rates of IGA success at this time were noted by the team as being 30.5% versus 9.4%, respectively (95% CI 10.3%-28.1%).

When the investigators looked at adverse events over the course of the treatment period, they reported occurrences in 71.7% of subjects given nemolizumab and 65.3% of those given a placebo. They added that most events had been of mild or moderate severity.

“These findings confirm effectiveness of targeting interleukin-31 signaling with nemolizumab in adults with moderate to severe [prurigo nodularis],” the investigators wrote.1

References

1. Ständer S, Yosipovitch G, Legat FJ, et al. Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis: The OLYMPIA 1 Randomized Clinical Phase 3 Trial. JAMA Dermatol. Published online November 27, 2024. doi:10.1001/jamadermatol.2024.4796.
2. Kwatra SG, Yosipovitch G, Ständer S, et al; OLYMPIA 2 Investigators. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. N Engl J Med. 2023 Oct 26;389(17):1579-1589. doi: 10.1056/NEJMoa2301333. PMID: 37888917.