The U.S. Food and Drug Administration (FDA) has accepted Galderma’s Biologics License Applications for nemolizumab for the treatment of patients with prurigo nodularis (PN) and for adolescents and adults with moderate to severe atopic dermatitis (AD).
In addition, the European Medicines Agency has also accepted the Marketing Authorization Applications for nemolizumab in prurigo nodularis and atopic dermatitis.
Nemolizumab is a first-in-class investigational monoclonal antibody specifically designed to inhibit IL-31 signaling to provide safe and rapid relief from the most burdensome symptom of both skin conditions: itch.
The FDA has granted nemolizumab Priority Review for prurigo nodularis. This follows its designation as a Breakthrough Therapy for the treatment of pruritus associated with prurigo nodularis, originally granted in December 2019 and reconfirmed in March 2023.
The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab in both prurigo nodularis and atopic dermatitis. Galderma is planning for multiple regulatory submissions in 2024.
“The relentless itch experienced by many people living with prurigo nodularis and atopic dermatitis has a significant impact on their overall quality of life,” says Baldo Scassellati Sforzolini, MD, PhD, the Global Head of R & D at Galderma, in a news release.
“We are thankful to the patients and medical experts whose insights informed our clinical trials, which assessed nemolizumab’s ability to reduce the symptoms of itch and skin lesions. We are one step closer to delivering this innovative solution to those in need and look forward to the outcomes of these filing decisions.”
The regulatory submissions of nemolizumab in prurigo nodularis are based on data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every four weeks in patients with prurigo nodularis.
Results from the OLYMPIA program demonstrated nemolizumab’s ability to rapidly improve itch, clear skin nodules and reduce sleep disturbance.
In the OLYMPIA program, patients treated with nemolizumab monotherapy showed clinically and statistically significant improvements in both primary endpoints compared to placebo after 16 weeks of treatment:
- More than half of nemolizumab-treated patients achieved an at least four-point reduction in itch intensity, as measured by the peak-pruritus numerical rating scale (PP-NRS; 58% and 56% in OLYMPIA 1 and 2, respectively, compared to 17% and 21% in the placebo groups).
- On average, a third of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions, when assessed using the investigator’s global assessment (IGA) score (26% and 38% in OLYMPIA 1 and 2, respectively, compared to 7% and 11% in the placebo groups; p<0.0001).
The trials also met all key secondary endpoints confirming rapid onset of action on itch and sleep disturbance within four weeks of treatment initiation:
- Fully 41% of nemolizumab-treated patients achieved an at least four-point reduction in itch in both the OLYMPIA 1 and 2 studies, as measured by the PP-NRS score, compared to 6% and 8% in the placebo groups, respectively.
- In OLYMPIA 2, nearly four times as many patients in the nemolizumab-treated group (37%) versus placebo (10%) achieved significant and clinically meaningful improvements in sleep disturbance, as measured by a four-point improvement on the sleep disturbance numerical rating scale.
The phase III OLYMPIA clinical trial program is the largest clinical trial program conducted in prurigo nodularis to date, with more than 500 patients enrolled, and the only one to include a long-term extension study.
The regulatory submissions of nemolizumab in atopic dermatitis are based on data from the phase III ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every four weeks in adolescents and adults with moderate to severe atopic dermatitis.
In the ARCADIA program, nemolizumab clinically improved skin lesions and rapidly improved itch and sleep disturbance.
Both ARCADIA trials showed clinically and statistically significant improvements in co-primary endpoints, compared to placebo, after 16 weeks of treatment:
- More than a third of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions when assessed using the IGA score (36% and 38% in ARCADIA 1 and 2, respectively, compared to 25% and 26% in the placebo groups).
- More than 40% of nemolizumab-treated patients achieved a 75% reduction in the Eczema Area and Severity Index (44% and 42% in ARCADIA 1 and 2, respectively, compared to 29% and 30% in the placebo groups).
The trials also met all key secondary endpoints confirming rapid onset of action on itch and sleep disturbance, with statistically significant and clinically meaningful improvements observed as early as one week after treatment initiation. Results at week 16 showed:
- Nearly half of nemolizumab-treated patients achieved an at least four-point reduction in itch intensity as measured by the PP-NRS score (49% and 48% in ARCADIA 1 and 2, respectively, compared to 21% in the placebo groups).
- Fully 44% and 38% of nemolizumab-treated patients in ARCADIA 1 and 2, respectively, achieved an at least four-point reduction in sleep disturbance as measured by the SD-NRS score (compared to 22% and 20% in the placebo group.
Nemolizumab was generally well tolerated and its safety profile was similar to placebo across the OLYMPIA and ARCADIA clinical trial programs.
Experts React
“It is very exciting news because it means that we may have nemolizumab approved in the United States within the next few months,” says Dermatology Digest Editorial Advisory Board Member Jonathan Silverberg, MD, PHD, MPH, a Professor, Director of Clinical Research, and Director of Patch Testing at George Washington University School of Medicine and Health Sciences in Washington, DC.
Ted Rosen, MD, Professor of Dermatology at Baylor College of Medicine in Houston and the Medical Editor of the Dermatology Digest, agrees. “This is the first step towards FDA approval for nemolizumab for management of Prurigo nodularis,” he says. “The data looks good, so barring any unexpected impediment, we expect this drug to be ultimately approved for that indication. That would provide us yet another therapeutic tool, with a different mechanism of action, to treat Prurigo nodularis, a heretofore difficult to manage modality. “
