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NEW ORLEANS – demonstrated.
Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.
After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.
Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.
Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
Primary, secondary endpoint results
Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).
As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
Adverse events
Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.
The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.
“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”
Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”
Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.
Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.
NEW ORLEANS – demonstrated.
Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.
After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.
Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.
Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
Primary, secondary endpoint results
Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).
As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
Adverse events
Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.
The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.
“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”
Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”
Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.
Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.
NEW ORLEANS – demonstrated.
Nemolizumab is a first-in-class investigational monoclonal antibody directed against the interleukin-31 receptor alpha that blocks signaling from IL-31. “From prior studies we know that it modulates pruritus, but also alters keratinocyte differentiation, inflammation, and fibrosis,” one of the investigators, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
OLYMPIA 2 was a phase 3, multicenter, double-blind study in adults with PN presenting with 20 or more nodules, and Investigator’s Global Assessment (IGA) score of 3 or more, and the Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7 or more. Exclusion criteria included chronic pruritus resulting from an active condition other than PN, such as neuropathic and psychogenic pruritus and active atopic dermatitis. In addition, the use of topical steroids, considered a rescue therapy, was not allowed in the trial, Dr. Kwatra said.
After an initial screening period, 274 patients at 73 sites in nine countries were randomized 2:1 either to the nemolizumab monotherapy or placebo. Following an initial 60-mg subcutaneous dose, patients received 30 mg or 60 mg (depending on their baseline weight) every 4 weeks for 16 weeks. The primary endpoint was the proportion of patients with a 4-point or greater improvement in the PP-NRS from baseline at week 16 and the proportion of patients with IGA success at week 16.
Selected key secondary endpoints included the proportion of patients with a 4 point or greater improvement from baseline in the PP-NRS at week 4, the Sleep Disturbance Numerical Rating Scale at week 4, and the SD-NRS at week 16. Safety endpoints included the incidence and severity of all adverse events.
Of the 274 patients randomized, 183 received nemolizumab and 91 received placebo. A total of 174 patients in the nemolizumab group completed the study, compared with 88 in the placebo group. The mean age of study participants was 53 years, 61% were women, 79% were White, 14% were Asian, and the rest were from other racial groups. More than half (57%) had IGA category 3 disease (moderate) and the remainder had IGA category 4 disease (severe); 63% had 20-100 lesions, and the remainder had more than 100. About one-third of study enrollees (32%) had a history of atopy.
Primary, secondary endpoint results
Dr. Kwatra reported that 56.3% of the patients in the nemolizumab group achieved a 4-point or greater improvement in the PP-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001), while 37.7% of those in the nemolizumab group achieved IGA success at week 16, compared with 11% of those in the placebo group (P < .0001).
As for secondary endpoints, 41% of patients in the nemolizumab group achieved a 4-point or greater improvement in PP-NRS at week 4, compared with 7.7% of those in the placebo group (P < .0001); and 37.2% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 4, compared with 9.9% of those in the placebo group (P < .0001). Almost 52% of patients in the nemolizumab group achieved a 4-point or greater improvement in SD-NRS at week 16, compared with 20.9% of those in the placebo group (P < .0001); and 9.8% of those in the nemolizumab group achieved IGA success at week 4, compared with 1.1% of those in the placebo group (P < .0074).
Adverse events
Treatment-emergent adverse events occurred in 61.2% of subjects in the nemolizumab group, compared with 52.7% of those in the placebo group. “There were no imbalances overall, [including] no injection-related reactions in either group,” Dr. Kwatra said. There was one case of newly diagnosed asthma in the placebo arm, and none in the treatment arm.
The researchers observed a slightly increased onset of atopic dermatitis in the treatment arm, compared with the placebo arm (5.5% vs. 0%). “Seven out of those 10 patients actually had a history of atopic dermatitis or high IgE [levels] and they were mostly managed with topical steroids without study drug discontinuation,” Dr. Kwatra added. Neurodermatitis, or worsening of PN, occurred in 3.8% of patients in the nemolizumab group, compared with 11% of those in the placebo group.
“The results of this study extend the efficacy and safety findings from the phase 2 study of nemolizumab in patients with PN,” Dr. Kwatra concluded. “I think they also help to usher in a new era of PN [treatment] in prime time.”
Kenneth B. Gordon, MD, who chairs the department of dermatology at the Medical College of Wisconsin, Milwaukee, and was asked to comment on the study, was impressed with nemolizumab’s propensity for blocking IL-31. “To be able to treat PN effectively by simply blocking the itch and not having a significant inflammatory function is really interesting,” he said in an interview at the meeting. If approved, nemolizumab “gives us another treatment option for a disease that is really debilitating. It’s very promising and we hope [the drug] will be available to us in the near future.”
Nemolizumab is being developed by Galderma. According to a press release from the company, nemolizumab was granted Breakthrough Therapy designation by the Food and Drug Administration in December 2019 for the treatment of pruritus associated with PN, a status that was reconfirmed in February 2023.
Dr. Kwatra disclosed that he is an advisory board member/consultant for Galderma, AbbVie, Amgen, Arcutis, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex, Incyte, Johnson and Johnson, Leo Pharma, Novartis, Pfizer, Regeneron, and Sanofi. Dr. Gordon disclosed that he is a consultant to, an investigator for, and/or a member of the advisory board for several pharmaceutical companies, but not Galderma.
AT AAD 2023