番茄社区

An investigational anti-interleukin (IL)-13 monoclonal antibody reduced eczema symptoms and was well-tolerated in adults with moderate to severe atopic dermatitis, a randomized phase II study showed.

At 16 weeks, a weekly 720-mg dose of cendakimab led to significantly greater improvements in mean Eczema Area and Severity Index (EASI) scores compared with placebo (mean change of -84.4% vs -62.7%, P=0.003), according to researchers led by Andrew Blauvelt, MD, of Oregon Medical Research Center in Portland.

The dose-ranging trial also showed numerically greater reductions in mean EASI scores versus placebo with the other two cendakimab regimens tested (720 mg or 360 mg, every 2 weeks), "but significance could not be claimed because the hierarchical testing sequence was interrupted," the team wrote in .

Key secondary endpoints also numerically favored the investigational drug.

Achievement of the primary endpoint "underscores the potential of cendakimab as a viable treatment option for patients suffering from this condition," Shoshana Marmon, MD, PhD, of New York Medical College in Valhalla, told 番茄社区.

"The findings also reinforce the established role of IL-13 as the primary cytokine driving type 2 inflammation linked to AD [atopic dermatitis]," added Marmon, who was not involved in the study.

Cendakimab selectively targets IL-13, binding to its receptors IL13R-α1 and IL13R-α2, explained Blauvelt and co-authors, who noted that "the intense itch associated with AD in the presence of IL-13 leads to scratch-related upregulation of IL-13Rα2 in keratinocytes that could promote lichenification."

With a crowded treatment landscape in atopic dermatitis, cendakimab's drugmaker Bristol Myers Squibb has indicated it for atopic dermatitis, though ongoing phase III studies are testing the anti-IL-13 monoclonal antibody for and , conditions also associated with type 2 inflammation.

Another IL-13 blocker, lebrikizumab, has already demonstrated benefit in atopic dermatitis in a trio of phase III trials, though the FDA last year , citing manufacturing concerns.

The double-blind phase II trial reported by Blauvelt and colleagues randomized 221 adults with moderate to severe atopic dermatitis in a 1:1:1:1 ratio to one of three dosing regimens of subcutaneous cendakimab (720 mg weekly, 720 mg every 2 weeks, or 360 mg every 2 weeks) or matching placebo.

The study was conducted from May 2021 to November 2022 at 69 sites in Canada, the U.S., the Czech Republic, Poland, and Japan. Eligible participants were required to have an inadequate response to topical medications, and use of drugs known to affect atopic dermatitis was prohibited during the trial other than for rescue purposes.

Patients enrolled had a mean age of 38 years, and 43% were women. A majority (62%) were white, more than a fourth (27%) were Asian, and 11% were Black. Average EASI score was 28.4 at baseline, with a mean disease duration of more than two decades. Approximately one-third of patients had a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score indicating severe disease (4 on the 0-4 scale) and about half had previously used systemic immunosuppressive agents.

The study's primary endpoint was mean change in EASI at 16 weeks. Key secondary endpoints included the proportion achieving a "clear" or "almost clear" score on vIGA-AD (0 or 1) and those with at least a 75% improvement in their EASI score (range 0-72, with higher scores indicating worse disease activity). Other endpoints included the proportion of patients achieving at least a 4-point reduction in Pruritus Numeric Rating Scale (P-NRS-4).

Among those randomized to cendakimab, 24-38% achieved a vIGA-AD score of 0 or 1 versus 9% of placebo recipients. Likewise, EASI-75 responders included 48-53% of participants on the study drug as compared with 26% of placebo patients.

P-NRS-4 response rates were similar across cendakimab treatment groups (33-35%) and also numerically greater than with placebo (15%), with effects observed as early as week 4 of treatment, according to Blauvelt and colleagues.

"Despite differences in dosing regimens and treatment duration, the proportion of patients achieving EASI-75, vIGA 0 or 1, and P-NRS-4 were overall similar to proportions from previous studies with that IL-13 function," they noted.

Rates of treatment-emergent adverse events (AEs) were comparable across treatment groups, ranging from 69-75% in the cendakimab arms versus 73% in the placebo arm -- most were mild or moderate in severity. Treatment discontinuation occurred in 1.8% of those assigned to the lowest cendakimab dosing regimen and 7.4% with the highest dose (720 mg weekly), as compared to 3.6% with placebo. A higher rate of serious treatment-emergent AEs were observed in the placebo group.

"Although not a specific concern with cendakimab, conjunctivitis cluster and herpes AEs have been observed in clinical trials of other agents that inhibit IL-13," Blauvelt and colleagues noted. In the current study, conjunctivitis cluster occurred in 11-18% of patients on cendakimab and 5% of those on placebo, while rates of herpes occurred in 4-6% and 2%, respectively.

Limitations of the study included high placebo response rates across the various endpoints, which may have been due to the required use of non-medicated topical emollients and rescue therapy, the authors said.

Comment