In the phase 2 study, all four doses of KHK4083/AMG 451 tested showed statistically greater improvements from baseline in Eczema Area and Severity Index (EASI) score at 16 weeks after subcutaneous administration compared with placebo.
"The data are exciting because this drug has the potential for disease modification beyond controlling the symptoms of the disease," lead investigator Dr. Emma Guttman-Yassky, Director of the Center for Excellence in Eczema at Mount Sinai, in New York City, told Reuters Health by phone.
She presented the results at the European Academy of Dermatology and Venereology 30th Virtual Congress.
"KHK4083/AMG 451 targets and inhibits the activity of the OX40 receptor expressed on the surface of effector T-cells, and has been shown to enhance the depletion of activated OX40+ T-cells by antibody-dependent cellular cytotoxicity (ADCC)," Kyowa Kirin Co., Ltd and Amgen, which are jointly developing the drug, explain in a news release announcing the phase 2 data.
"It has been reported that effector T-cells expressing OX40 are present in the lesions of patients with atopic dermatitis and are critical in the disease pathophysiology," they write.
The phase 2 results demonstrate that "inhibition and deletion of the OX40-expressing cells may provide an important new approach to treating moderate-to-severe atopic dermatitis, with the potential to help patients maintain responses," Dr. Yoshifumi Torii, with Kyowa Kirin, said in the release.
This randomized, double-blind, placebo-controlled study enrolled 274 adults in the U.S., Japan, Canada, and Germany with moderate-to-severe atopic dermatitis who were not adequately controlled with topical agents.
The study tested four doses of subcutaneously administered KHK4083/AMG 451: 600 mg once every two weeks (Q2W), or four weeks (Q4W), 300 mg Q2W, or 150 mg Q4W.
Compared with placebo, improvement from baseline to week 16 in the EASI score for the four active treatment groups were 54.7%, 49.7%, 61.1%, and 48.3%, respectively.
"The nice thing was at all the doses results were significant compared to placebo - and when all the doses are working compared to placebo, this is usually when we know that the drug works, so I was happy to see that," Dr. Guttman-Yassky told Reuters Health.
Compared to placebo, treatment with KHK4083/AMG 451 also led to improvements at week 16 in several key secondary endpoints, including achieving at least a 75% reduction from baseline in EASI score (EASI-75), an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least 2-point reduction from baseline (IGA 0/1) and at least a 4-point reduction from baseline in pruritus Numerical Rating Scale (NRS) score (PNRS-4).
"What's super exciting," Dr. Guttman-Yassky said, is that after the drug was stopped most patients on the higher doses maintained the EASI-75 response during 20 weeks follow-up. "That is what I call disease modification, and this is really the first real disease-modification signal that we have with any drug for atopic dermatitis."
The most commonly reported side effects seen in at least 5% of patients were pyrexia, nasopharyngitis, worsening of atopic dermatitis, and chills. The events of pyrexia and chills were mild to moderate in intensity and did not lead to discontinuation of treatment.
"Atopic dermatitis affects over 30 million people a year and is known to have an extremely negative impact on patients' lives," Dr. David M. Reese, with Amgen, said in the release.
"These data provide strong evidence of the potential of KHK4043/AMG 451 for patients, and we look forward to studying this treatment further in Phase 3 clinical trials, which we expect to begin in the first half of 2022," he added.
The study was funded by Kyowa Kirin and Amgen. Dr. Guttman-Yassky is the leading investigator of the study and a paid consultant for the KHK4083/AMG 451 development by Kyowa Kirin.
SOURCE: https://bit.ly/2WTHbpF European Academy of Dermatology and Venereology 30th Virtual Congress, presented October 2, 2021.
By Megan Brooks
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