WASHINGTON — More than half of patients with chronic spontaneous urticaria (CSU) had complete symptom control for a year or longer with the anti-IgE antibody ligelizumab, extension data from a randomized trial showed.
During the first 12 weeks of the extension study, 52.2% of patients treated with ligelizumab attained a score of 0 on the 7-day urticaria activity score (UAS7). Those clearance rates were maintained during the first 52 weeks of follow-up in the extension phase, which will continue for a total of 104 weeks, Diane Baker, MD, of Baker Allergy, Asthma, and Dermatology Clinic in Portland, Oregon, reported here at the American Academy of Dermatology meeting.
The findings came from an open-label extension of a randomized trial that compared multiple doses of ligelizumab with placebo and omalizumab (Xolair) in patients with CSU uncontrolled by H1 antihistamines. As previously reported, ligelizumab led to significantly better CSU control at 12 weeks as compared with omalizumab. Patients with active disease at week 12 could switch to ligelizumab 240 mg Q4W (N=201) and continue treatment for as long as 2 years.
Results of the randomized phase IIb trial and extension provided the basis for two randomized phase III trials involving 2,000 patients with inadequately controlled CSU. Patients will be randomized to one of two doses of ligelizumab, omalizumab, or placebo. Both trials have the same primary endpoint: change in UAS7 from baseline to week 12.
The study was one of several early-stage trials that yielded favorable results in patients with various types of dermatologic conditions.
BTK Inhibitor Active in Pemphigus
A majority of patients with pemphigus vulgaris attained disease control within the first month of treatment with the oral Bruton’s tyrosine kinase (BTK) inhibitor PRN1008, according to results of a small phase II trial.
By week 4 of treatment, 14 of 26 patients had achieved disease control, defined as no new lesions and evidence of healing in existing lesions while on daily low-dose corticosteroids (≤0.5 mg/kg). After 12 weeks, 19 patients met criteria for disease control, as reported by DeDee Murrell, MD, of the University of New South Wales in Sydney.
Additionally, four patients had complete remission by week 12 (secondary endpoint) and a fourth of the patients were in complete remission at 24 weeks. Complete remission had a median duration of about 2 months, and the time to relapse from disease control or complete remission after 12 weeks of treatment ranged from 27 to ≥99 days.
Pemphigus arises from development of autoantibodies to desmoglein (DSG) 1 and 3, Murrell noted. BTK inhibition interrupts multiple immune-cell signaling pathways in immune cells, but not in T cells. In the phase II trial, treatment response correlated with reductions in titers of the pathogenic autoantibodies.
Early Activity Signal With Anti-IL-36 Drug for Psoriasis
A monoclonal antibody targeting interleukin (IL)-36 led to rapid improvement in signs and symptoms of generalized pustular psoriasis as well as reductions in associated gene expression and inflammatory infiltrates, a proof-of-concept study showed.
Pustules in three of the seven study participants were completely cleared within the first 2 days of treatment with BI-655130, and in six of the patients by week 2, according to results presented here and published in a Correspondence in the New England Journal of Medicine.
The mean improvement from baseline on the Generalized Pustular Psoriasis Area and Severity Index was 59.0% in the first week and 79.8% by week 4, and all improvements were maintained up to week 20.
Laboratory assessments at 1 week, reported at a symposium on atopic dermatitis and related conditions by James G. Krueger, MD, PhD, of Rockefeller University in New York City, showed reductions of as much as 94% in expression of genes associated with the innate immune axis. Other laboratory evidence of early improvement included reductions of:
- 24%-64% in IL-36 and IL-17 gene expression
- 25%-87% in expression of genes associated with neutrophil attractant chemokine/chemokine receptor
- 55%-202% in neutrophil-associated gene expression
- 30%-54% expression of IL-20-associated genes
Krueger said the results supported the role of IL-36-related mechanisms in generalized pustular psoriasis, of IL-36 inhibition as a therapeutic strategy for the condition, and showed that BI-655130 activity occurred independently of IL36RN mutation status.
The ligelizumab study was supported by Novartis.
Baker disclosed relationships with Novartis.
The pemphigus study was sponsored by Principia.
Murrell disclosed relationships with Principia, Roche, GlaxoSmithKline, and Novartis.
The study of pustular psoriasis was supported by Boehringer Ingelheim.
Krueger disclosed relationships with Boehringer Ingelheim, AbbVie, Baxter, Biogen Idec, Delenex, Kineta, Sanofi, Serono, XenoPort, Amgen, Bristol-Myers Squibb, Dermira, Innovaderm, Janssen, Kadmon, Kyowa, Lilly, Merck, Novartis, Parexel, and Pfizer.