Bermekimab improves all disease measures of atopic dermatitis in phase 2 study
Bermekimab, which neutralizes interleukin-1 alpha, improved all disease measures of atopic dermatitis, including a large reduction in pruritus, according to phase 2 trial results presented at the European Academy of Dermatology and Venereology Congress by Alice Gottlieb, MD, PhD, of Icahn School of Medicine at Mount Sinai.
“Dermatologists have not been exposed to treatments targeting anti-IL-1 alpha. They need to learn about IL-1 in the skin and what it does,” Gottlieb told Healio Dermatology. “They now have a potential new tool in their toolbox to treat diseases like atopic dermatitis and hidradenitis suppurativa with a new class of medications targeting IL-1, which is novel.”
In the open-label, proof-of-concept, multicenter study, 10 patients with moderate to severe atopic dermatitis received weekly 200 mg bermekimab (XBiotech) subcutaneous injections for 4 weeks while 28 patients received weekly 400 mg bermekimab subcutaneous injections for 8 weeks.
“We target IL-1 alpha. It was the first cytokine,” John Simard, founder, president and CEO at XBiotech, said in an interview. “We have the only antibody that is derived from a natural human response. It’s the only antibody that targets IL-1 alpha, which blocks activation of the blood vessels, which is the first step in a lot of inflammation.”
All disease measures showed significant improvement in the 400 mg group, and better improvements in clinical outcomes were seen in this group compared with the 200 mg group, according to the meeting abstract. After 8 weeks in the 400 mg group, Dermatology Life Quality Index (DLQI) decreased 72% from baseline, Eczema Area and Severity Index decreased 79%, Global Individual Signs Score decreased 57%, Hospital Anxiety and Depression Scale (social anxiety) decreased 68%, Hospital Anxiety and Depression Scale (depression) decreased 65%, Patient Oriented Eczema Measure decreased 71% and Scoring Atopic Dermatitis decreased 67% (all P < .0001).
Additionally, by week 8, 78% of patients achieved a 4 point or greater improvement in pruritus-Numerical Rating Scale (NRS) worst scores and 80% achieved a 4 point or greater improvement in average itch scores, according to the abstract.
“The FDA likes to look at subjects that achieved greater than 4 points in NRS score reduction in itch,” Gottlieb said.
Almost one-third of patients (29%) had a 2 point or greater improvement in Investigator Global Assessment score and achieved a score of 0 or 1 by week 8, according to the abstract.
“When I first heard about the study, it wasn’t intuitive to me that IL-1 alpha would be a key player in atopic dermatitis,” Gottlieb said. “The two things that supported it were that in adults, T-helper 1 immunity does play a significant role in adults with chronic atopic dermatitis, and we know that anti-IL-17C, which has been reported to be effective in atopic dermatitis, affects keratinocytes in the release of IL-1 alpha.”
“The speed and extent of the response surprised us,” Simard said. “We anticipated a good outcome, but how fast and extensive it was surprised us. We are achieving DLQI in half the time. People are getting better so much quicker than what we’ve seen in the past.”
Previous research has been published on bermekimab results in hidradenitis suppurativa, psoriasis and acne vulgaris, according to Simard.
“Ultimately, this is going to be a multifaceted dermatologic product,” he said. – by Abigail Sutton
Gottlieb A. Bermekimab is a rapid and effective treatment for atopic dermatitis, including marked reduction in pruritis. Presented at: 28th European Academy of Dermatology and Venereology Congress; Oct. 9-13, 2019; Madrid.
Disclosures: Gottlieb reports she consults for XBiotech. Simard reports he is founder, president and CEO of XBiotech and owns stock in the company.