CSU: Ligelizumab likely safe and effective for adolescents

Ligelizumab as a treatment for adolescents with chronic spontaneous urticaria (CSU) insufficiently controlled with antihistamines did not raise new safety concerns in a phase 2b study. The small study found an exposure-response relationship consistent with that of adults.

“Ligelizumab is a next-generation, high-affinity, humanised, monoclonal anti-IgE antibody, which results in rapid, strong, and sustained symptom control in adult patients,” Prof. Bülent Şekerel (Hacettepe University, Turkey) said in his introduction [1]. In adults, the agent led to a high rate of complete CSU control that was superior to omalizumab and placebo [2].

The current international, randomised-controlled study (NCT03437278) investigated ligelizumab in a dose-finding phase 2b trial. Patients ≥12 and <18 years of age were randomised to placebo or ligelizumab (24 mg or 120 mg, every 4 weeks) over 24 weeks and a follow-up until week 40. Participants in the placebo arm were switched to 120 mg of ligelizumab at week 12. The focus of the trial was on safety, pharmacokinetics, the exposure-response relationship, and the efficacy profile. However, with 49 adolescents entering the study, there was no sufficient power to determine differences between treatment arms.

Baseline data included a mean age of 14.8 years, 57.1% women, and a mean bodyweight of 61.0 kg. The participants suffered from CSU for an average of nearly 3 years and had all been refractory to H₁-antihistamines. Treatment with 120 mg of ligelizumab was numerically superior to placebo. Moreover, the rate of patients with complete response, equalling a weekly Urticaria Activity Score (UAS) of 0, was greatest with the higher dose of the active drug and reached 61.5% at week 24. “After accounting for a bodyweight effect on clearance and other parameters, no additional age effect could be detected,” explained Prof. Şekerel. Thus, the clearance of ligelizumab was influenced by body weight but not by age.

“Ligelizumab was well tolerated and no new safety signals were observed at any dose in the adolescent patients,” Prof. Şekerel pointed out. Overall, 77.6% of patients experienced at least 1 adverse event. Most common were nasopharyngitis and headache. Two serious adverse events were reported; both were not linked to the study drug.

“In conclusion, in this study, ligelizumab exhibited an efficacy profile in adolescent patients with CSU consistent with that known in adults and the similarity in ligelizumab pharmacokinetics and model-estimated potency may support the use of the same dose for treatment for CSU in both adolescents and adults,” Prof. Şekerel summarised. The phase 3 PEARL1 (NCT03580356) and PEARL2 (NCT03580369) studies will further evaluate ligelizumab’s efficacy.

1. 
   
   1. Şekerel BE. Efficacy, safety and pharmacokinetics of ligelizumab: Results from a dedicated Phase 2b study in adolescent patients with chronic spontaneous urticarial. D3T01.1A, EADV Congress 2021, 29 Sept–2 Oct.
   2. Maurer M, et al. N Engl J Med. 2019 Oct 3;381(14):1321-1332.

 

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Posted on 18 November 202127 March 2024