D2.503 - LP-003 Injection for the treatment of H1 Antihistamine-Inadequately Controlled Chronic Spontaneous Urticaria (CSU): A Multicenter, Randomized, Double-Blind, Controlled Phase Ⅱ Study

A substantial number of patients with CSU still have poorly controlled symptoms despite standard-of-care H1 antihistamine therapy, representing a clear unmet clinical need. LP-003, a next-generation anti-IgE monoclonal antibody, was developed to improve IgE neutralization via enhanced inhibition of FcεRI binding, higher affinity, and extended half-life versus omalizumab.A substantial number of patients with CSU still have poorly controlled symptoms despite standard-of-care H1 antihistamine therapy, representing a clear unmet clinical need. LP-003, a next-generation anti-IgE monoclonal antibody, was developed to improve IgE neutralization via enhanced inhibition of FcεRI binding, higher affinity, and extended half-life versus omalizumab.

Adult participants with CSU refractory to H1-antihistamines were enrolled in this randomized, double-blind, Phase Ⅱ study (NCT06228560). Participants were assigned (1:1:1:1:1) to receive LP-003 (100 mg Q8W, 200 mg Q8W, or 200 mg Q4W), omalizumab (300 mg Q4W), or placebo, as add-on therapy to stable-dose second-generation H1 antihistamines. The endpoints included proportion of participants achieving complete control (UAS7=0), mean change of UAS7 from baseline at Week 12, and other efficacy and safety endpoints.

Among 202 participants enrolled, at Week 12, a total of 44.4%, 66.7%, and 57.5% for the participants treated with LP-003 100 mg Q8W, 200 mg Q8W, and 200 mg Q4W, respectively, had complete control (UAS7=0), as compared with 43.6% for omalizumab and 10.3% for placebo. All LP-003 groups showed significant superiority over placebo (all p<0.001); notably, the LP-003 200 mg Q8W group significantly outperformed omalizumab (difference Δ23.1%, p=0.0405). Least squares (LS) mean reductions in UAS7 at Week 12 were -23.15, -26.63, and -24.74 for LP-003 doses, compared with -21.85 for omalizumab and -13.98 for placebo. All LP-003 regimens resulted in significantly greater UAS7 reductions than placebo (all p<0.0001), and LP-003 200 mg Q8W yielded a significantly greater reduction versus omalizumab (difference Δ-4.78; p=0.0137). The pooled 200 mg group (Q8W + Q4W) also demonstrated superior activity over omalizumab (difference Δ-3.82, p=0.0223). Rapid onset of efficacy was evident by Week 4, with LS mean UAS7 reductions of -16.72, -20.99, -20.55, -16.32 and -8.35 in LP-003 100 mg Q8W, 200 mg Q8W, 200 mg Q4W, omalizumab and placebo, respectively. Furthermore, LS mean UAS7 reduction in LP-003 pooled 200 mg group showed superior efficacy over omalizumab (Δ-4.45, p=0.0392). TEAEs were mostly mild or moderate, with no treatment-related serious events.

LP-003 provided robust, rapid and sustained symptom control in CSU with a superior activity over omalizumab and favorable safety profile, offering a promising treatment alternative for participants with uncontrolled CSU.