Eye on OX40 in AD: Rocatinlimab Performs Well in Two Phase 2 Trials

Rocatinlimab demonstrated a significant reduction in IgE concentrations and clinical efficacy measures in patients with moderate–severe AD.

OX40 is considered a new potential treatment target in atopic dermatitis (AD), and two new studies of the investigational anti-OX40 monoclonal antibody rocatinlimab may add weight to the evidence.

Rocatinlimab inhibits and reduces the number of OX40+ pathogenic T cells responsible for driving systemic and local AD inflammatory responses. The initial antibody was discovered in collaboration between Kyowa Kirin US Research and La Jolla Institute for Immunology. On June 1, 2021, Kyowa Kirin and Amgen entered into an agreement to jointly develop and commercialize rocatinlimab.

In one study, Rocatinlimab demonstrated a significant reduction in IgE concentrations in addition to clinical efficacy measures in patients with moderate–severe atopic dermatitis.

This double-blind, placebo-controlled Phase 2 trial randomized patients (n=274) 1:1:1:1:1 to subcutaneous rocatinlimab 150 or 600mg every 4 weeks (Q4W), 300 or 600mg every 2 weeks (Q2W) for 36 weeks, or placebo (Weeks 0–18; rocatinlimab 600mg Q2W Weeks 18–36), and a 20-week off-treatment follow-up period (Week 56).

Overall, 267 patients comprised the full analysis set; rocatinlimab: n=210 (78.7%), placebo: n=57 (21.3%). Rocatinlimab decreased mean serum IgE concentrations below baseline by Week 16(P ≤ 0.0005). These reductions continued to Week 36 and were maintained to Week 56.

In the placebo group, mean serum IgE concentrations increased to Week 16. After switching to 600mg Q2W at Week 18, concentrations decreased to Week 36 and continued to decrease below baseline to Week 56. Mean IgE reductions at Weeks 16, 36 and 56 were: -19.7%, -38.9%, -26.7% (150mg Q4W); -17.1%, -39.5%, -46.5% (600mg Q4W); -18.6%, -44.8%, -10.9% (300mg Q2W); -16.9%, -48.6%, -58.5% (600mg Q2W); 34.2%, -8.8%, -29.1% (placebo/600mg Q2W).

Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers, and nausea.

In a second study, rocatinlimab demonstrated improvements in patient-reported outcomes in adults with moderate–severe atopic dermatitis.

This Phase 2b, multicenter, double-blind, placebo-controlled trial, randomly assigned adult patients to subcutaneous rocatinlimab every 4 weeks (Q4W; 150 or 600mg) or every 2 weeks (300 or 600mg) or placebo, for 18 weeks, followed by an 18-week active treatment extension and a 20-week off-treatment follow-up (Week 56). Patient-reported outcomes (PROs) included pruritus and sleep disturbance (SD) scores, measured using a (Numerical Rating Scale (NRS), and the Dermatology Life Quality Index (DLQI). These were assessed at baseline to Week 16 and until Week 56.

Overall, 267 patients were randomized (rocatinlimab: n=210; placebo: n=57). From baseline to Week 16, percentage reductions in NRS-pruritus (p≤0.029) and NRS-SD scores (p≤0.025) were greater in the rocatinlimab groups compared with placebo. Improvement in pruritus and SD scores in the rocatinlimab groups was maintained until Week 56.

Greater reductions in DLQI scores in the rocatinlimab groups compared with placebo up to Week 16 (all p<0.05) were observed; scores continued to improve in the rocatinlimab groups to Week 36 and were maintained during the off-treatment period.

Treatment emergent adverse events (TEAEs) were reported for 175 of 216 (81.0%) subjects in rocatinlimab groups and 41 of 57 (71.9%) subjects in the placebo group in the initial 18-week double-blind treatment period. The most frequent TEAEs, reported in ≥ 10% of subjects in the combined rocatinlimab groups were nasopharyngitis, worsening of AD, pyrexia and chills. TEAEs of pyrexia and chills were mild to moderate in intensity and were mostly observed only after the first administration of rocatinlimab without resulting treatment discontinuation. There were no hypersensitivity reactions or deaths.

Both studies were presented at the 2023 annual meeting of the American Academy of Dermatology in New Orleans.