Rocatinlimab improves disease severity in patients with moderate to severe head and neck disease
skin disease (H&N AD), a post-analysis of a Phase IIb trial showed.
“The H&N area is more exposed to environmental triggers and may be more difficult to treat than any other parts of the body… [Thus, AD in this region] “It puts an emotional burden on patients,” said Dr. Emma Guttman-Yasky of the Icahn School of Medicine in Mount Sinai, New York City, New York, US, at EADV 2022.
“Rocatinlimab is the first anti-OX40 monoclonal antibody that targets important pathways underlying the pathogenesis of Alzheimer’s disease,” she continued. It reduces the number of T cells that express OX40 and can attenuate the local and systemic inflammation that drive Alzheimer’s pathology. [J Dermatol Sci 2020;99:82-89] “[Rocatinlimab] It may be an effective treatment for Alzheimer’s disease…including resistant, hard-to-treat manifestations of H&N,” said Guttmann-Yasky.
The study included 274 adults with moderate to severe chronic Alzheimer’s disease (EASI mean *>30) who had an inadequate response or intolerance to topical Alzheimer’s disease treatment. Of these, 219 patients with H&N AD (mean EASI >3) were included in the post hoc analysis. Participants were randomized 1:1:1:1:1 to receive SC rocatinlimab 150 or 600 mg Q4W, 300 or 600 mg Q2W for 36 weeks, or placebo for the first 18 weeks and then switch to rocatinlimab 600 mg Q2W from week 18 To 36 this was followed by a 20-week period of off-drug follow-up. [EADV 2022, abstract 3587]
At week 16, H&N EASI scores improved significantly with all doses of rocatinlimab compared to placebo. For the 300 and 600 mg doses, least squares mean baseline percentage changes ranged from -59 to -65 (versus -17 with placebo; P<0.001 for all comparisons). For the 150 mg dose, the percentage change for LSM was -44, which was still greater than that seen with placebo (P = 0.008). These results are consistent with those observed in the primary analysis.
Week 24 saw an in-depth look at the responses. In the rocatinlimab placebo arm, the change at week 16 of LSM in the H&N EASI score jumped to -29. When other rocatinlimab doses were compared with the rocatinlimab placebo arm, LSM changes remained greater, and more so with higher doses (–65, -68, and -78 versus 300 mg, 600 mg Q4W, and 600 mg Q2W, respectively.; p≤0.001 for all). These responses are further deepened by week 36.
“Importantly, rocatinlimab caused long-term responses,” Guttmann-Yaske continued, regarding results for Week 56. “It is noteworthy that after week 36, patients no longer received the drug. [yet] There was persistence of responses for an additional 20 weeks in a difficult-to-treat area such as the face.”
In the full analysis group (placebo-controlled phase), the most common adverse events resulting from treatment with rocatelinlimab were fever, nasopharyngitis, exacerbation of Alzheimer’s disease, and chills. “It is noteworthy that nasopharyngitis and exacerbations of Alzheimer’s disease were more prevalent in the placebo arm,” Guttmann-Yaske said. In the post-analysis, no new safety signals were observed. There were no new H&N lesions.
Unique mechanism of action
“This is the first evidence that anti-OX40 monoclonal antibodies improve disease severity in patients with difficult-to-treat H&N AD,” said Guttmann-Yaske. She noted that although patients often had an acute spectrum, all doses of rocatelinimab had success in improving H&N EASI scores from baseline.
“[The current findings suggest that rocatinlimab] It may be beneficial for H&N AD… and thus may improve H&N lesions in AD without the challenges seen with IL-4 inhibitors,”
“[The] The robustness of the response with rocatinlimab is unique among current Alzheimer’s therapies, likely reflects the unique mechanism of action, and may suggest disease modification, Guttmann-Yaske said. Thus, rocatinlimab represents a potential new treatment option for [H&N] ad.”