REPORTING FROM AAD 2018
SAN DIEGO (FRONTLINE MEDICAL NEWS) – An anti–interleukin-33 antibody aimed at atopic dermatitis performed reasonably well in a small, proof-of-concept phase 2a study, and will proceed along its developmental pathway.
All 12 patients who received one intravenous infusion of ANB020 achieved at least a 50% reduction in their Eczema Area and Severity Index (EASI) by day 29, Graham Ogg, MD, said at the annual meeting of the American Academy of Dermatology. Most of the improvement occurred in the first 2 weeks, was largely sustained for 2 months, then gradually began to fade, said Dr. Ogg, professor of dermatology at Oxford University, England.
The EASI improvement, along with improvements in itch and clinical assessment, are enough to propel ANB020 into a phase 2b, placebo-controlled, randomized trial, which Dr. Ogg said would recruit 200 to 300 adults with moderate to severe atomic dermatitis (AD).
ANB020 is a selective inhibitor of interleukin-33 (IL-33), which is highly expressed in the lesions of AD, Dr. Ogg said. “IL-33 is produced by a number of cells, including keratinocytes and epithelial cells. It’s an alarm molecule predominately produced after damage to keratinocytes; for example, after an allergenic challenge to the skin.”
The antibody has already passed its phase 1 trials, which included both a fixed and ascending dose study of 10 mg to 750 mg in healthy adults. ANB020 has a long half-life of 16 days after IV infusion or subcutaneous injection, inhibits IL-33 for up to 85 days, and has no apparent dose-limiting toxicities.
The phase 2a study comprised 12 adults (mean age 40 years) with a mean EASI score of 32, Dr. Ogg reported. The mean Investigator’s Global Assessment score was 4, and the mean Severity Scoring of Atopic Dermatitis almost 65. Patients had high itch scores and scored a mean of 13 on the Dermatology Life Quality Index. All were inadequately controlled on topical corticosteroids, and about half had failed at least one systemic immunomodulator.
Following a washout period, all subjects received an initial placebo infusion, and 1 week later received a single 300-mg infusion of ANB020. The primary endpoint – at least a 50% reduction in EASI score (EASI-50) – was assessed at day 29, with close follow-up until day 140.
By day 15, nine patients (75%) had achieved EASI-50, and three (25%) had achieved a 75% reduction in EASI score (EASI-75). The average EASI score reduction was 58% at that point. By day 29, 10 (83%) had achieved EASI-50, and 4 (33%), EASI-75. This benefit was largely maintained until day 78, when it began to tail off somewhat. By day 140, five patients (42%) still had an EASI-50 and three (25%), an EASI-75.
Three patients (25%) achieved an Investigator’s Global Assessment score of 0 or 1, indicating clear or almost clear skin. On day 29, the average pruritus decrease was 32%, which dropped to 21% by day 140. The average Severity Scoring of Atopic Dermatitis reduction was 40% on day 29 and 32% on day 140. The average Dermatology Life Quality Index reduction was 45% on day 29 and 43% on day 140.
ANB020 was well tolerated with no drug-related safety signals. Dizziness occurred in 17% of subjects, and mild headache in 25%. There was one serious adverse event, a case of major depression that occurred on day 140. This was consistent with the patient’s baseline health history and deemed unrelated to the study drug.
According to an AnaptysBio press release , ANB020 is also being investigated in a double-blind, placebo-controlled study of 20 adults with severe peanut allergy. The company also is enrolling a 24-patient randomized, double-blind, placebo-controlled, phase 2a trial in adults with severe eosinophilic asthma.
Topline data from both of these studies are expected soon, the website noted.
AnaptysBio funded Dr. Ogg’s travel and registration fees for the meeting. He said he had no other financial disclosures relevant to ANB020.
SOURCE: Ogg G et al. AAD 2018. Abstract 6658.