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Dr. Marcus Maurer
“For sure, ligelizumab is the highlight of this year in urticariology,” Marcus Maurer, MD, declared at the annual congress of the European Academy of Dermatology and Venereology. An ongoing phase 3 trial will now compare more than 1,000 patients with CSU who will be randomized to ligelizumab, omalizumab, or placebo.
Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, and this translated into greater therapeutic efficacy in the multicenter, double-blind, placebo-controlled clinical trial, explained Dr. Maurer, professor of dermatology and allergy at Charité University in Berlin.
Study participants, all refractory to histamine1 antihistamines and in many cases to leukotriene receptor antagonists as well, were randomized to omalizumab at 300 mg, placebo, or to ligelizumab at 24 mg, 72 mg, or 240 mg administered by subcutaneous injection every 4 weeks for 20 weeks. The study showed that the effective dose of ligelizumab lies somewhere between 72 and 240 mg; the 24-mg dose won’t be pursued in further studies.
“Three things are important in the comparison between ligelizumab and omalizumab: First, ligelizumab works faster – and omalizumab is a fast-working drug in urticaria. As early as week 4 after initiation of treatment, ligelizumab resulted in a significantly higher response rate,” he said.
Second, a complete response rate as defined by an Urticaria Activity Score over the past 7 days (UAS7) of 0 was achieved by more than 50% of patients on ligelizumab at 240 mg, a rate twice that seen in the omalizumab group. Indeed, more patients were symptom-free on ligelizumab at 72 mg or 240 mg than on omalizumab throughout the 20-week study.
And third, time to relapse after treatment discontinuation was markedly longer with ligelizumab.
“Once you stop the treatment, we expect patients to come back because we didn’t cure the disease, we blocked the signs and symptoms by blocking mast cell degranulation. Relapse after the last injection occurred at about 4 weeks with omalizumab versus 10 weeks for ligelizumab on average. That’s amazing,” Dr. Maurer said.
At week 20, the mean reductions from baseline in UAS7 scores were 13.6 points with placebo, 15.2 points with the lowest dose of ligelizumab, 18.2 points with omalizumab, 23.1 points with ligelizumab at 72 mg, and 22.5 points for ligelizumab at 240 mg.
The side effect profiles for both biologics were essentially the same as for placebo with the exception of a 5.9% rate of mild injection site reactions with ligelizumab at the 240-mg dose versus 2.3% with placebo.
Many clinicians have noticed a significant limitation of omalizumab: It is less effective in patients with more complex CSU having an autoimmune overlay, type 2b angioedema, and/or long disease duration.
“This does not seem to be the case with ligelizumab. Even for the difficult-to-treat subpopulations of CSU, ligelizumab appears to be a drug that can protect against mast cell degranulation. We see a reduction in angioedema activity; we see a reduction in wheal size and number; we see a reduction in the itch – so across all the symptoms in the difficult subpopulations, this is the better drug. Now we have to make it work in the phase 3 trials to bring it to clinical practice,” he said.
Dr. Maurer reported receiving research funding from and serving as an advisor to and paid speaker for Novartis, which markets omalizumab and is developing ligelizumab.