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Remibrutinib, an investigational Bruton's tyrosine kinase (BTK) inhibitor, was safe and efficacious in patients with chronic spontaneous urticaria (CSU), a phase IIb extension study showed.

In nearly 200 patients who received at least one dose of remibrutinib, complete response to treatment, measured by a weekly Urticaria Activity Score (UAS7) of zero, was observed in 28.2% at 4 weeks and 55.8% at 52 weeks, reported Vipul Jain, MBBS, of McMaster University in Ontario, Canada, and co-authors.

In addition, well-controlled disease (UAS7≤6) was seen in 52.7% and 68% at these time points, they noted in the .

Most treatment-emergent adverse events (TEAEs) were mild or moderate and considered unrelated to remibrutinib by the researchers.

Previous results from a dose-finding study presented at the American Academy of Dermatology meeting showed that as many as a fourth of patients with CSU had complete responses within the first week of starting remibrutinib, increasing to 41.9% by week 12.

"The favorable safety and tolerability profile and sustained efficacy with long-term exposure of remibrutinib 100 mg [twice daily] for up to 52 weeks in this study supports the continued development of remibrutinib in patients with CSU inadequately controlled with H1-antihistamines," Jain and colleagues wrote. "Remibrutinib thus could be a potential new oral treatment option for patients with CSU that offers fast disease control with a favorable safety profile."

After 4 weeks, mean UAS7 scores had changed from baseline measurements by an average of -17.6 points. By 12 weeks, scores had changed by -19.4 points, and by week 52, by -21.8 points. "Clinical improvement was rapid, with reductions in UAS7 from baseline observed as early as week 1 (-14.8)," the authors noted.

Overall, 71.6% of patients reported at least one TEAE, with 35.1% reporting at least one mild or moderate TEAE, including infestation and infection, skin and subcutaneous tissue disorders, and gastrointestinal disorders.

Severe TEAEs were reported by 4.1% of patients, and included appendicitis, upper abdominal pain, muscle strain, muscle spasms, COVID-19 pneumonia, nephrolithiasis, and osteonecrosis. Just under 6% of the participants withdrew from the study due to TEAEs.

This extension study included 194 patients; average age was 45.5, 71.6% were women, 78.4% were white, and 19.6% were Asian. Mean duration of CSU was 5.8 years.

Patients who had a weekly UAS7 of less than 16 entered a treatment-free observational period for no more than 12 weeks. Second-generation H1-antihistamines were allowed for patients to use as a kind of "background therapy," if necessary, but only after the first 4 weeks of the study.

"Remibrutinib treatment was highly effective in patients with CSU who had completed the core study but had either not achieved a UAS7 below 16 during the core study or relapsed during the treatment-free follow-up period of the core study or during the observational period of the extension study," Jain and team wrote. "The results suggest that remibrutinib is efficacious in the treatment of patients with CSU, and if stopped and restarted, the response is comparably faster than the initial treatment phase."

They noted that the lack of a placebo group in the study may have limited the findings. However, phase III clinical trials for remibrutinib are currently underway to better understand the drug's safety and efficacy.

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